Science.gov

Sample records for 10-14 cm3 s-1

  1. 24 CFR 10.14 - Hearings.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 1 2011-04-01 2011-04-01 false Hearings. 10.14 Section 10.14... RULEMAKING: POLICY AND PROCEDURES Procedures § 10.14 Hearings. (a) The provisions of 5 U.S.C. 556 and 557, which govern formal hearings in adjudicatory proceedings, do not apply to informal rule...

  2. 24 CFR 10.14 - Hearings.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Hearings. 10.14 Section 10.14... RULEMAKING: POLICY AND PROCEDURES Procedures § 10.14 Hearings. (a) The provisions of 5 U.S.C. 556 and 557, which govern formal hearings in adjudicatory proceedings, do not apply to informal rule...

  3. Adaptation of California Measure of Mental Motivation-CM3

    ERIC Educational Resources Information Center

    Özdemir, Hasan Fehmi; Demirtasli, Nükhet Çikrikçi

    2015-01-01

    Education without doubt, plays a vital role for individuals to gain the essential personal traits of the 21st century, also known as "knowledge age". One of the most important skills among these fundamental qualities which the individuals should be equipped with is critical thinking. California Measure of Mental Motivation-CM3 was…

  4. 15 CFR 10.14 - Appeals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... PRODUCT STANDARDS § 10.14 Appeals. (a) Any person directly affected by a procedural action taken by NIST... hearing the appeal will develop a recommendation to the Committee concerning the resolution of the appeal. NIST will review the recommendation and if found acceptable will subject it to a letter ballot of...

  5. The amino acid sequence of protein CM-3 from Dendroaspis polylepis polylepis (black mamba) venom.

    PubMed

    Joubert, F J

    1985-01-01

    Protein CM-3 from Dendroaspis polylepis polylepis venom was purified by gel filtration and ion exchange chromatography. It comprises 65 amino acids including eight half-cystines. The complete amino acid sequence of protein CM-3 has been elucidated. The sequence (residues 1-50) resembles that of the N-terminal sequence of the subunits of a synergistic type protein and residues 51-65 that of the C-terminal sequence of an angusticeps type protein. Mixtures of protein CM-3 and angusticeps type proteins showed no apparent synergistic effect, in that their toxicity in combination was no greater than the sum of their individual toxicities. PMID:4029488

  6. 43 CFR 10.14 - Lineal descent and cultural affiliation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    .... 10.14 Section 10.14 Public Lands: Interior Office of the Secretary of the Interior NATIVE AMERICAN... Hawaiian organization or by the common law system of descendence to a known Native American individual... shared group identity that may be reasonably traced historically or prehistorically between a...

  7. 43 CFR 10.14 - Lineal descent and cultural affiliation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    .... 10.14 Section 10.14 Public Lands: Interior Office of the Secretary of the Interior NATIVE AMERICAN... Hawaiian organization or by the common law system of descendence to a known Native American individual... affiliation between present-day individuals and Indian tribes or Native Hawaiian organizations and...

  8. On line Coupling of Aerosole Thermodynamic Model with RegCM3

    NASA Astrophysics Data System (ADS)

    Shalaby, Ahmed; Zakey, Ashraf

    2010-05-01

    Development of RegCM3 to be a comprehensive an On-line climate-chemistry model run through two phase. Phase one include coupling of gas-phase chemistry and Second phase include coupling of Aerosole Thermodynamic model. Here ISOROPPIA is coupled with RegCM3 to calculate the composition and phase state of ammonia, sulfate, nitrate, chloride, sodium, calcium, potassium, magnisium, water inorganic aerosole in thermodynamic equilibrium with gas phase precursor. The coupling include only the direct effect of aerosols. The simulation has been done over Northern Africa and Mediterranean region to study the effect of new aerosoles chemistry on the radiation field and how such aerosoles affect the concentration of surface ozone.

  9. The influence of vegetation on the ITCZ and South Asian monsoon in HadCM3

    NASA Astrophysics Data System (ADS)

    McCarthy, M. P.; Sanjay, J.; Booth, B. B. B.; Krishna Kumar, K.; Betts, R. A.

    2012-06-01

    The role of global vegetation on the large-scale tropical circulation is examined in the version 3 Hadley Centre climate model (HadCM3). Alternative representations of global vegetation cover from observations and a dynamic global vegetation model (DGVM) were used as the land-cover component for a number of HadCM3 experiments under a nominal present day climate state, and compared to the simulations using the standard land cover map of HadCM3. The alternative vegetation covers result in a large scale cooling of the Northern Hemisphere extra-tropics relative to the HadCM3 standard, resulting in a southward shift in the location of the inter-tropical convergence zone (ITCZ). A significant reduction in Indian monsoon precipitation is also found, which is related to a weakening of the South Asian monsoon circulation, broadly consistent with documented mechanisms relating to temperature and snow perturbations in the Northern Hemisphere extra-tropics in winter and spring, delaying the onset of the monsoon. The role of the Northern Hemisphere extra-tropics on tropical climate is demonstrated, with an additional representation of vegetation cover based on DGVM simulated changes in Northern Hemisphere vegetation from the end of the 21st Century. This experiment shows that through similar processes the simulated extra-tropical vegetation changes in the future contribute to a strengthening of the South Asian monsoon in this model. These findings provide renewed motivation to give careful consideration to the role of global scale vegetation feedbacks when looking at climate change, and its impact on the tropical circulation and South Asian monsoon in the latest generation of Earth System models.

  10. Moisture characteristics over Indian region during Summer Monsoon using RegCM3

    NASA Astrophysics Data System (ADS)

    Janardanan, Rajesh; Rajanayagam, Lorna; Mohanakumar, Kesavapillai

    In this study, the spatial characteristics of the total Precipitable Water during monsoon season over Indian region, based on the sensitivity experiments performed by a regional climate model for an anomalously dry year. The present study uses a recent version (Version-III) of National Center for Atmospheric Research (NCAR) Regional Climate Model (RegCM3). RegCM3 has been integrated at 60 km horizontal resolution over the Indian domain. The planetary boundary layer scheme used is that of Holtslag, cumulus parameterization scheme Emanuel of MIT, SUBEX large scale precipitation scheme and BATS ocean flux parameterization scheme. The model is run from 1st May to 30th September. The first month is taken for the spin up. The next four months are taken to study the monsoon. The experiments are carried out by increasing the initial conditions of Sea Surface Temperature by steps of 0.1 degree ranging up to 1degree. The change in the Total Precipitable water and their spatial distribution are studied. The zonal and meridional moisture transports are also analysed. The features simulated by RegCM3 are compared with those of the NCEP/NCAR reanalysis. Key words:- Peninsular India, model integration, Monsoon Rainfall Reference: K. C. chow, Yiming Liu, Johnny C. L. Chan and Yihui Ding, Int. J. Climatol. 26: 1339-1359 (2006) K. C. Chow, Hang-Wai Tong and Johnny C. L. Chan, Clim. Dyn. DOI 10.1007/s00382-007- 0301-6 G. P. Singh, Jai-Ho Oh, Jin-Young Kim and Ok-Yeon Kim; ", SOLA, Vol. 2, pp.29-32 (2006) Dash S. K., Shekhar M. S., Singh G. P. Theoretical and Applied Climatology 86(1-4): 161 (2006)

  11. The influence of vegetation on the ITCZ and South Asian Monsoon in HadCM3

    NASA Astrophysics Data System (ADS)

    McCarthy, M. P.; Sanjay, J.; Booth, B. B. B.; Krishna Kumar, K.; Betts, R. A.

    2012-02-01

    The role of extra-tropical vegetation on the large-scale tropical circulation is examined in the version 3 Hadley Centre Climate Model (HadCM3). Alternative representations of present day vegetation from observations and a dynamic vegetation model were used as the land-cover component for a number of HadCM3 experiments under a nominal present day climate state, and are shown to induce perturbations to the simulated global dynamics. This results in a shift in the location of the Inter Tropical Convergence Zone (ITCZ) and changes in the South Asian monsoon circulation. This has a significant impact on the Indian land precipitation compared to the standard configuration of HadCM3. This large-scale forcing is consistent with documented mechanisms relating to temperature and snow perturbations in the Northern Hemisphere extra-tropics. This analysis demonstrates that uncertainties in the representation of present day vegetation cover can result in significant perturbations to the simulated climate. The role of the Northern Hemisphere extra-tropics is further demonstrated with a fourth representation of vegetation cover produced by imposing simulated changes in Northern Hemisphere extra-tropical vegetation from the end of the 21st century on the present day climate. This experiment shows that through similar processes extra-tropical vegetation changes in the future contribute to a strengthening of the South Asian monsoon in this model, with a particular influence on the monsoon onset. These findings provide renewed motivation to give careful consideration to the role of global scale vegetation feedbacks when looking at climate change and its impact on the tropics and South Asian monsoon in the latest generation of Earth System models.

  12. Parameterization Measurements of a 963 cm3 LaBr3:Ce Crystal

    NASA Astrophysics Data System (ADS)

    Marsh, J. C.; Litz, M. S.; Chiara, C. J.; Carroll, J. J.

    2015-04-01

    LaBr3:Ce is a relatively new scintillator with characteristics that surpass more commonly used radiation detection scintillators. Published results for small (< 10 cm3) LaBr3 detectors (NIMA 683, 46, 2012) describe improved time resolutions (~ 35 ps), energy resolutions (~3.5% at 662 keV), and optical yields (~63,000 photons/MeV) compared to NaI and BGO. Here it was possible to assess the characteristics of a 963 cm3 (7.6 cm length, 12.7 cm diameter) cylindrical crystal optically coupled to an ET9390KB photomultiplier tube optimized for crystal emissions at 380 nm. A 3 × 3 array of crystals will be used for neutron-stimulated evaluations of materials for elemental and chemical composition. A custom bleeder chain was designed to minimize current saturation and optimize the energy linearity over a 2-12 MeV energy range. Because large volume crystal characteristics do not always scale linearly, energy resolution, detector efficiency, crystal homogeneity, timing resolution, pulse shape, peak-to-Compton ratios, energy linearity, and self activity were all measured and compared to published results on other LaBr3 detectors. Advantages and disadvantages of such large LaBr3 crystals will be discussed, and future plans will be described. This work was supported by the Army Research Laboratory under Cooperative Agreement W911NF-12-2-0019.

  13. Recent and future changes in Arctic sea ice simulated by the HadCM3 AOGCM

    NASA Astrophysics Data System (ADS)

    Gregory, J. M.; Stott, P. A.; Cresswell, D. J.; Rayner, N. A.; Gordon, C.; Sexton, D. M. H.

    2002-12-01

    The HadCM3 AOGCM has been used to undertake an ensemble of four integrations from 1860 to 1999 with forcings due to all major anthropogenic and natural climate factors. The simulated decreasing trend in average Arctic sea ice extent for 1970-1999 (-2.5% per decade) is very similar to observations. HadCM3 indicates that internal variability and natural forcings (solar and volcanic) of the climate system are very unlikely by themselves to have caused a trend of this size. The simulated decreasing trend in Arctic sea ice volume (-3.4% per decade for 1961-1998) is less than some recent observationally based estimates. Extending the integrations into the 21st century, Arctic sea ice area and volume continue to decline. Area decreases linearly as global-average temperature rises (by 13% per K), and volume diminishes more rapidly than area. By the end of the century, in some scenarios, the Arctic is ice-free in late summer.

  14. Relationship between tropospheric temperature and Indian summer monsoon rainfall as simulated by RegCM3

    NASA Astrophysics Data System (ADS)

    Pattnayak, K. C.; Panda, S. K.; Saraswat, Vaishali; Dash, S. K.

    2016-05-01

    Relationship between rainfall and tropospheric temperature (TT) has been examined over the Indian subcontinent during four seasons of the year using Regional Climate Model Version 3.0 (RegCM3). The model has been integrated at 55 km horizontal resolution over India during the years 1980-2000 with prescribed lateral boundary forcing from the 40 years re-analysis (ERA40) of the European Centre for Medium-range Weather Forecasts. Results of this study show that RegCM3 in general is able to capture the spatial distributions of rainfall in all the seasons as compared to the corresponding IMD0.5 gridded rainfall. The model has simulated warmer TT over the Himalayan region in all the seasons as compared to ERA40. However, it is well captured over the peninsular India and the oceanic regions. In the model, larger warming by about 0.5 °C over the northwest and Central India in the summer monsoon months might have lead to lower surface pressure there. Also, the vertical extent of the monsoon trough is found to be up to 500 hPa in the model as compared to that in NCEP/NCAR reanalysis. As a consequence, the simulated monsoon circulation and rainfall are stronger than those observed. The two most important rainfall seasons, the summer monsoon and winter are reasonably well simulated with correlation coefficients (CC) of 0.60 and 0.59 respectively significant at 99 % confidence level with the corresponding observed values of IMD0.5. Further, Indian summer monsoon rainfall (ISMR) and TT during the contrasting monsoon years are also close to their respective observed values. Temporal CCs between the TT over Tibet, Pakistan and Central India during the summer monsoon season and gridded ISMR values reveals that the TT over Pakistan has been better correlated with the ISMR than those over Tibet and Central India. This relationship has been well supported by the model simulations.

  15. Unravelling the Drivers of the Recent Drought over Sao Paulo (Brazil) using HadCM3

    NASA Astrophysics Data System (ADS)

    Pattnayak, K. C.; Tindall, J. C.; Brienen, R.; Baker, J.; Spracklen, D. V.; Gloor, E. U.

    2015-12-01

    Since ca. 2010, Sao Paulo has struggled with a multi-year drought. Reservoir levels of Sao Paulo, south-America's largest city, are at a record low level, and as a result the city has implemented water-controlling measures. Usually, the rainy season runs from October through March, bringing important rain for this city. However, over the last 5 years, Sao Paulo has experienced multiple years of below average rainfall. In this study, we try to explain the climatic drivers and mechanisms behind the observed drought over Sao Paulo using a combination of observations and model simulations. We analyse observed precipitation, air temperature and sea surface temperature (SST) datasets over the recent past to characterise the climate anomalies and visualize the extent of the drought. We then use the Hadley Centre Climate model (HadCM3) with prescribed observed SST anomalies to probe the possible causes behind the drought. This analysis will show us possible climatic drivers behind the drought in the most densely populated region of South America.

  16. Improvement of surface albedo parameterization within a regional climate model (RegCM3)

    NASA Astrophysics Data System (ADS)

    Bao, Y.; Lü, S.

    2009-03-01

    A parameterization for calculating surface albedo of Solar Zenith Angel (SZA) dependence with coefficient for each vegetation type determined on the Moderate Resolution Imaging Spectro-radiometer (MODIS) reformed by the Bidirectional Reflectance Distribution Function (BRDF) is incorporated within the latest Abdus Salam International Centre for Theoretical Physics (ICTP) Regional Climate Model (RegCM3), and evaluated with a high resolution one-way nesting simulation in China using the Climate Research Unit (CRU) data and the observations from the Field Experiment on Interaction between Land and Atmosphere in Arid Region of Northwest China (NWC-ALIEX). The performance of the SZA method modeling surface characteristic is investigated.Results indicate, RegCM with SZA method (RCM_SZA) considerably improve the cold bias of original RegCM (RCM_ORI) in air surface temperature in East Asia with 1.2 degree increased in summer due to the lower albedo produced by SZA method which makes more solar radiation absorbed by the surface and used for heating the atmosphere near to the surface. The simulated diurnal cycle of ground temperature conforms fairly well to the observation in the nesting simulation in Northwest China, especially during the noon time when the SZA has the lowest value. However, the modification can not obviously affect the East Asia summer monsoon precipitation simulation although RCM_SZA produce more evapo-transpiration in surface with more than 2 Wm-2 increases in simulated latent heat fluxes both in East Asia and in Northwest China compared to RCM_ORI.

  17. Evaluation and analysis of RegCM3 simulated summer rainfall over the Huaihe River Basin of China

    NASA Astrophysics Data System (ADS)

    Zong, Peishu; Wang, Huijun

    2011-06-01

    This study evaluates the ability of the Abdus Salam International Center for Theoretical Physics (ICTP) version 3 Regional Climate Model (RegCM3) in simulating the summer rainfall amount and distribution and large-scale circulation over the Huaihe River basin of China. We conducted the simulation for the period of 1982-2001 and the wet year of 2003 to test the ensemble simulation capacity of RegCM3. First, by comparing the simulated rainfall amount and distribution against the observations, it is found that RegCM3 can reproduce the rainfall pattern and its annual variations. In addition, the simulated spatial patterns of 850-hPa wind and specific humidity fields are close to the observations, although the wind speed and humidity values are larger. Finally, the ensemble simulation of RegCM3 for summer 2003 failed to capture the spatial distribution and underestimated the magnitude of the precipitation anomalies, and the reasons are analyzed.

  18. Sensitivity of ICTP Regional Climate Model (RegCM3) to Initial and Lateral Boundary Conditions

    NASA Astrophysics Data System (ADS)

    Nadeem, I.; Formayer, H.

    2009-04-01

    Regional climate simulations require lateral boundary conditions. These are typically reanalysis of past observations or alternatively, output from climate general circulation models. Lateral boundary conditions are available at various temporal and spatial resolutions. At present, spatial resolution of reanalysis datasets ranges from few kilometers, for example, regional reanalysis limited to only single continent, to the coarser but global datasets like ECMWF 40 Years Re-Analysis. While these datasets represent reasonable analyses of 3-D atmospheric as well as surface conditions, their resolutions, the physics of the models used to generate them, and the means of assimilating data into them can produce very different results when used as boundary conditions for regional climate models. The sensitivity of ICTP Regional Climate Model (RegCM3) to different lateral boundary conditions was investigated over the Alpine region. The model was run directly at 10km horizontal resolution as well as in one-way double nested mode, with a 30 km grid point spacing mother domain encompassing the Europe and a 10 km grid point spacing nested domain covering the Alpine Region. The simulations spans the one-year period of 1989. The boundary conditions used for various simulations were ECMWF Interim Re-Analysis (ERA-Interim, 0.75° and 1.5° grid spacings, 6-h intervals), the ECMWF 40 Years Re-Analysis (ERA40, 1° and 2.5° grid spacings, 6-h interval) and finally the 2.5°, 6-h NCEP/DOE AMIP-II Reanalysis (Reanalysis-2). Sea Surface Temperature for the simulated periods were obtained from a UK Met Office Global Ocean Surface Temperature (GISST), a set of SST data in monthly 1° area grids. When recently released ERA-Interim Reanalysis, which is based on a recent release of the Integrated Forecasting System (IFS Cy31r2) containing many improvements both in the forecasting model and analysis methodology, was used as lateral and boundary conditions, the simulated precipitation field

  19. High resolution climate change simulation of the 21st century over East Asia by RegCM3

    NASA Astrophysics Data System (ADS)

    Gao, Xuejie

    2010-05-01

    To meet the increasing demands from the climate change impact assessment studies, a high resolution climate change simulation over East Asia region has being performed in the National Climate Center of the China Meteorological Administration. The model employed in the study is the Abdus Salam International Centre for Theoretical Physics (ICTP) Regional Climate Model (RegCM3). A global model of the CCSR/NIES/FRCGC MIROC3.2_hires is selected to drive RegCM3 because of its high resolution (T106) and its good performances in simulating the present day climate over the region. The simulation is conducted at 25-km grid spacing for the period of 1951-2100. Observed CO2 concentration are used for the present day simulation of 1951-2000 and the emission scenario of IPCC SRES A1B is used as the GHG (greenhouse gases) forcing. Simulations of present day climate over China by RegCM3 and MIROC3.2_hires are compared against observation to valid the model performances. Results show that both models reproduced the general pattern of surface air temperature and precipitation well over the region. Compared to the driving MIROC3.2_hires, RegCM3 provides with more spatial details of the surface fields. Differed from previous GCM-RegCM3 simulations, the RegCM3 did not improves the general pattern of the precipitation due to the good performances of MIROC3.2_hires. Preliminary analysis of the future changes simulated by the two models' show difference, in particular during June-July-August. For example while the MIROC3.2_hires projected a prevailing increase of precipitation in JJA over China, the RegCM3 projected extended areas of decreased precipitation. The data are available for those interested from the community of climate change impacts studies.

  20. 46 CFR 30.10-14 - Combination carrier-TB/ALL.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 1 2011-10-01 2011-10-01 false Combination carrier-TB/ALL. 30.10-14 Section 30.10-14 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-14 Combination carrier—TB/ALL. The term combination carrier means a tank vessel designed to...

  1. 46 CFR 30.10-14 - Combination carrier-TB/ALL.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 1 2010-10-01 2010-10-01 false Combination carrier-TB/ALL. 30.10-14 Section 30.10-14 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS GENERAL PROVISIONS Definitions § 30.10-14 Combination carrier—TB/ALL. The term combination carrier means a tank vessel designed to...

  2. An Exploratory Pilot Study of the Strengthening Families Programme 10-14 (UK)

    ERIC Educational Resources Information Center

    Coombes, Lindsey; Allen, Deborah Mary; Foxcroft, David

    2012-01-01

    The Strengthening Families Programme 10-14 (SFP10-14; UK) is a seven-session DVD-based family skills training programme. While the programme has been extensively evaluated in the United States, no randomized controlled trial (RCT) of the SFP10-14 has been conducted in the United Kingdom. This exploratory Phase II study was an evaluation of a…

  3. Sensitivity of the GCM driven summer monsoon simulations to cumulus parameterization schemes in nested RegCM3

    NASA Astrophysics Data System (ADS)

    Sinha, P.; Mohanty, U. C.; Kar, S. C.; Dash, S. K.; Kumari, S.

    2013-04-01

    The regional climate model (RegCM3) from the Abdus Salam International Centre for Theoretical Physics has been used to simulate the Indian summer monsoon for three different monsoon seasons such as deficit (1987), excess (1988) and normal (1989). Sensitivity to various cumulus parameterization and closure schemes of RegCM3 driven by the National Centre for Medium Range Weather Forecasting global spectral model products has been tested. The model integration of the nested RegCM3 is conducted using 90 and 30-km horizontal resolutions for outer and inner domains, respectively. The India Meteorological Department gridded rainfall (1° × 1°) and National Centre for Environment Prediction (NCEP)-Department of Energy (DOE) reanalysis-2 of 2.5° × 2.5° horizontal resolution data has been used for verification. The RegCM3 forced by NCEP-DOE reanalysis-2 data simulates monsoon seasons of 1987 and 1988 reasonably well, but the monsoon season of 1989 is not represented well in the model simulations. The RegCM3 runs driven by the global model are able to bring out seasonal mean rainfall and circulations well with the use of the Grell and Anthes-Kuo cumulus scheme at 90-km resolution. While the rainfall intensity and distribution is brought out well with the Anthes-Kuo scheme, upper air circulation features are brought out better by the Grell scheme. The simulated rainfall distribution is better with RegCM3 using the MIT-Emanuel cumulus scheme for 30-km resolution. Several statistical analyses, such as correlation coefficient, root mean square error, equitable threat score, confirm that the performance of MIT-Emanuel scheme at 30-km resolution is better in simulating all-India summer monsoon rainfall. The RegCM3 simulated rainfall amount is more and closer to observations than that from the global model. The RegCM3 has corrected its driven GCM in terms of rainfall distribution and magnitude over some parts of India during extreme years. This study brings out several

  4. Implantation technique of the 50-cm3 SynCardia Total Artificial Heart: does size make a difference?

    PubMed

    Spiliopoulos, Sotirios; Guersoy, Dilek; Dimitriou, Alexandros Merkourios; Koerfer, Reiner; Tenderich, Gero

    2015-01-01

    Despite downsizing, implantation technique of the 50-cm(3) SynCardia Total Artificial Heart and settings of the Companion driver remain unchanged. Owing to the absence of de-airing nipples, de-airing procedure is even more crucial and has to be performed carefully. PMID:26438624

  5. New α-adrenergic property for synthetic MTβ and CM-3 three-finger fold toxins from black mamba.

    PubMed

    Blanchet, Guillaume; Upert, Gregory; Mourier, Gilles; Gilquin, Bernard; Gilles, Nicolas; Servent, Denis

    2013-12-01

    Despite their isolation more than fifteen years ago from the venom of the African mamba Dendroaspis polylepis, very few data are known on the functional activity of MTβ and CM-3 toxins. MTβ was initially classified as a muscarinic toxin interacting non-selectively and with low affinity with the five muscarinic receptor subtypes while no biological function was determined for CM-3. Recent results highlight the multifunctional activity of three-finger fold toxins for muscarinic and adrenergic receptors and reveal some discrepancies in the pharmacological profiles of their venom-purified and synthetic forms. Here, we report the pharmacological characterization of chemically-synthesized MTβ and CM-3 toxins on nine subtypes of muscarinic and adrenergic receptors and demonstrate their high potency for α-adrenoceptors and in particular a sub-nanomolar affinity for the α1A-subtype. Strikingly, no or very weak affinity were found for muscarinic receptors, highlighting that pharmacological characterizations of venom-purified peptides may be risky due to possible contaminations. The biological profile of these two homologous toxins looks like that one previously reported for the Dendroaspis angusticeps ρ-Da1a toxin. Nevertheless, MTβ and CM-3 interact more potently than ρ-Da1a with α1B- and α1D-AR subtypes. A computational analysis of the stability of the MTβ structure suggests that mutation S38I, could be involved in this gain in function. PMID:23648423

  6. Tellurite-, tellurate-, and selenite-based anaerobic respiration by strain CM-3 isolated from gold mine tailings.

    PubMed

    Maltman, Chris; Piercey-Normore, Michele D; Yurkov, Vladimir

    2015-09-01

    The newly discovered strain CM-3, a Gram-negative, rod-shaped bacterium from gold mine tailings of the Central Mine in Nopiming Provincial Park, Canada, is capable of dissimilatory anaerobic reduction of tellurite, tellurate, and selenite. CM-3 possesses very high level resistance to these oxides, both aerobically and anaerobically. During aerobic growth, tellurite and tellurate resistance was up to 1500 and 1000 µg/ml, respectively. In the presence of selenite, growth occurred at the highest concentration tested, 7000 µg/ml. Under anaerobic conditions, resistance was decreased to 800 µg/ml for the Te oxides; however, much like under aerobic conditions, growth with selenite still took place at 7000 µg/ml. In the absence of oxygen, CM-3 couples oxide reduction to an increase in biomass. Following an initial drop in viable cells, due to switching from aerobic to anaerobic conditions, there was an increase in CFU/ml greater than one order of magnitude in the presence of tellurite (6.6 × 10(3)-8.6 × 10(4) CFU/ml), tellurate (4.6 × 10(3)-1.4 × 10(5) CFU/ml), and selenite (2.7 × 10(5)-5.6 × 10(6) CFU/ml). A control culture without metalloid oxides showed a steady decrease in CFU/ml with no recovery. ATP production was also increased in the presence of each oxide, further indicating anaerobic respiration. Partial 16S rRNA gene sequencing revealed a 99.0 % similarity of CM-3 to Pseudomonas reactans. PMID:26254805

  7. Sensitivity of simulated extreme precipitation and temperature to convective parameterization using RegCM3 in China

    NASA Astrophysics Data System (ADS)

    Hui, Pinhong; Tang, Jianping; Wang, Shuyu; Wu, Jian

    2015-10-01

    In this study, the regional climate model of RegCM3 is applied to investigate the sensitivity of regional climate over China using four cumulus parameterizations, the modified Anthes-Kuo (AK), the Grell with Arakawa-Schubert closure, the Grell with Fritsch-Chappell closure, and the MIT-Emanuel (EM). The model was integrated over the period of 1982 to 2001 using the NCEP Reanalysis data NNRP2 as boundary conditions. RegCM3 coupled with various cumulus parameterizations is evaluated firstly as for its ability to represent regional climatology and climate extreme indices, and the results show that simulated regional climate in China is sensitive to the option of cumulus parameterizations. All the cumulus schemes produce a northward expansion of heavy rain area and an underestimation of surface air temperature. For precipitation, the AK scheme simulates relatively better magnitude, while the EM scheme has more reliable performance on the spatial distribution. RegCM3 can represent the spatial distributions of extreme indices for both precipitation and temperature, as well as their decadal trends irrelevant to the cumulus parameterizations. However, the model underestimates the consecutive dry days and overestimates the three extreme wet indices, with the EM scheme giving the worst result. Slight underestimations of extreme temperature indices are detected in all cumulus parameterization scheme runs. The shapes of probability distribution functions for extreme indices are correctly produced, though the probabilities of extreme dry and warm events are underestimated.

  8. 19 CFR 10.14 - Fabricated components subject to the exemption.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Fabricated components subject to the exemption. 10.14 Section 10.14 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY; DEPARTMENT OF THE TREASURY ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. General Provisions Articles Assembled Abroad with...

  9. Late 20th century attribution of drying trends in the Sahel from the Regional Climate Model (RegCM3)

    NASA Astrophysics Data System (ADS)

    Jenkins, Gregory S.; Gaye, Amadou T.; Sylla, Bamba

    2005-11-01

    The RegCM3 has been integrated for the period of 1960-2002 using initial and lateral boundary conditions from the NCEP re-analyses at 6-hour intervals. Greenhouse gas concentrations remain fixed and the land-use/soil properties are not altered. The RegCM3 accurately portrays a trend from wetter conditions in the 1960s to very dry conditions in the 1980s. The dry 1980s temperatures in the Sahel are approximately 3°K warmer than the wet 1960s, caused by a reduction in precipitation and clouds leading to an increase in the net absorbed solar radiation at the surface. This anomalous warming maintains the steepest meridional temperature gradient and therefore the African Easterly Jet in lower latitudes. The initiation of dry conditions starts in June and persists through July and August in the model simulations. The initiation of dry conditions appears to be related to a weaker Tropical Easterly Jet which may be linked to warmer Indian Ocean temperatures over the past several decades.

  10. Perovskite CH3NH3PbI3(Cl) Single Crystals: Rapid Solution Growth, Unparalleled Crystalline Quality, and Low Trap Density toward 10(8) cm(-3).

    PubMed

    Lian, Zhipeng; Yan, Qingfeng; Gao, Taotao; Ding, Jie; Lv, Qianrui; Ning, Chuangang; Li, Qiang; Sun, Jia-Lin

    2016-08-01

    Single crystal reflects the intrinsic physical properties of a material, and single crystals with high-crystalline quality are highly desired for the acquisition of high-performance devices. We found that large single crystals of perovskite CH3NH3PbI3(Cl) could be grown rapidly from chlorine-containing solutions. Within 5 days, CH3NH3PbI3(Cl) single crystal as large as 20 mm × 18 mm × 6 mm was harvested. As a most important index to evaluate the crystalline quality, the full width at half-maximum (fwhm) in the high-resolution X-ray rocking curve (HR-XRC) of as-grown CH3NH3PbI3(Cl) single crystal was measured as 20 arcsec, which is far superior to so far reported CH3NH3PbI3 single crystals (∼1338 arcsec). The unparalleled crystalline quality delivered a low trap-state density of down to 7.6 × 10(8) cm(-3), high carrier mobility of 167 ± 35 cm(2) V(-1) s(-1), and long transient photovoltaic carrier lifetime of 449 ± 76 μs. The improvement in the crystalline quality, together with the rapid growth rate and excellent carrier transport property, provides state-of-the-art single crystalline hybrid perovskite materials for high-performance optoelectronic devices. PMID:27458057

  11. Deionization of Dopants in Silicon Nanofilms Even with Donor Concentration of Greater than 10(19) cm(-3).

    PubMed

    Tanaka, Takahisa; Kurosawa, Yuya; Kadotani, Naotoshi; Takahashi, Tsunaki; Oda, Shunri; Uchida, Ken

    2016-02-10

    Understanding the dopant properties in heavily doped nanoscale semiconductors is essential to design nanoscale devices. We report the deionization or finite ionization energy of dopants in silicon (Si) nanofilms with dopant concentration (ND) of greater than 10(19) cm(-3), which is in contrast to the zero ionization energy (ED) in bulk Si at the same ND. From the comparison of experimentally observed and theoretically calculated ED, we attribute the deionization to the suppression of metal-insulator transition in highly doped nanoscale semiconductors in addition to the quantum confinement and the dielectric mismatch, which greatly increase ED in low-doped nanoscale semiconductors. Thus, for nanoscale transistors, ND should be higher than that estimated from bulk Si dopant properties in order to reduce their resistivity by the metal-insulator transition. PMID:26741540

  12. Investigating Tectonic Drivers of Miocene - Pliocene Polar Climate Evolution using the HadCM3 Climate Model.

    NASA Astrophysics Data System (ADS)

    Hunter, S. J.; Knies, J.; Haywood, A. M.; Dolan, A. M.; Pound, M. J.

    2015-12-01

    We model the climate of the Miocene (Tortonian and the Messinian) and the Pliocene (Piacenzian) using the HadCM3 Atmosphere-Ocean GCM. We use baseline Miocene and Pliocene geographies that have different reconstruction lineages so we describe methods to create a set of self-consistent paleogeographies that represent the main features of the three stages. We present large-scale features of the evolving climate and examine model fidelity by comparing modelled climatology against palaeoenvironmental proxy data. We focus on the climate of the Arctic region and investigate tectonic drivers of sea ice expansion by comparing and interpreting model predictions against borehole data from the North Atlantic and Arctic Ocean. In particular how Late Miocene/ early Pliocene tectonic uplift in the Svalbard/Barents Sea and Greenland region, the opening of the Bering Strait, and the onset of deep water Atlantic-Arctic exchange influenced the development of modern sea ice cover.

  13. Drug Ingestions in Children 10-14 Years Old: An Old Problem Revisited

    ERIC Educational Resources Information Center

    Pomerantz, Wendy; Gittelman, Michael; Farris, Sarah; Frey, Lauren

    2009-01-01

    To determine changes in rates of drug ingestions in 10-14 year old children in our country, a retrospective chart review of 10-14 year olds hospitalized for drug ingestion between 1993-1995 and 2000-2004 was performed. Odds ratios and Chi-square were used for analyses. From 1993-1995 there were 92.8 ingestions/100,000 children/year; from 2000-2004…

  14. Sensitivity of the simulated African monsoon of summers 1993 and 1999 to convective parameterization schemes in RegCM3

    NASA Astrophysics Data System (ADS)

    Tchotchou, L. A. Djiotang; Kamga, F. Mkankam

    2010-03-01

    In this study, the International Center for Theoretical Physics Regional Climate Model version 3 (RegCM3) was used to investigate the sensitivity of the simulation of the West African monsoon using four different cumulus and closures parameterization schemes of Anthes Kuo (AK), Grell and Fristish Chappell (GFC), Grell and Arakawa Schubert (GAS), and MIT-Emmanuel (EM) while maintaining other physical packages unchanged. The contrasting monsoon years of 1993 and 1999, which were dry and wet years, respectively, were simulated. The model was integrated from a period of 5 months, starting from May 1 to September 30 of each year using the European Centre for Medium-Range-Weather Forecast (ECMWF) Reanalysis data (ERA40) as input boundary conditions. The 6-hourly reanalysis data were used to provide the lateral boundary conditions, and the observed weekly Reynolds Sea Surface Temperature interpolated to 6 h was used as the lower boundary forcing. The results show that in West Africa, monsoon precipitations are sensitive to the choice of cumulus parameterization and closure schemes. None of the schemes is able to simulate the monsoon rainfall accurately, and furthermore, there is little difference in behavior among schemes between dry and wet years. The spatial features of precipitation are not identical among schemes, although they all show a northward shift of the rain bands, giving a very wet Sahel and dry Guinean Coast. The GFC and EM schemes are able to capture the diurnal cycle of precipitation and the zonal averages of stratiform rain fractions as observed in the Tropical Rainfall Measuring Mission (TRMM), although they overestimated rainfall amounts. The most important deficiencies, however, cannot be attributed to the schemes. In particular, the northward shift of both the rain band and the AEJ in RegCM3 is the result of unrealistic soil moisture resulting from the way albedo is parameterized, leading to an excessive northward penetration of monsoon flow. A

  15. Regional Climate Responses To Planetary-Scale Geoengineering Activities, as Modeled Using climateprediction.net/HadCM3L

    NASA Astrophysics Data System (ADS)

    Ricke, K.

    2009-12-01

    Concerns that climate mitigation is occurring too slowly, or that there may be a rapid "climate surprise," have lead to renewed dialogue within the scientific community about cooling the planet through geoengineering, specifically stratospheric albedo modification (SAM). There is little consensus about regional hydrological effects of such activities despite a recent spate of climate modeling studies looking at its potential impacts. Here we present the results from one large-ensemble experiment that used Hadley Centre Coupled Model, version 3 with reduced resolution over the ocean (HadCM3L), implemented through climateprediction.net. The analysis examines 54 globally-uniform stratospheric optical depth modification scenarios designed to stabilize global temperatures under SRES A1B. We present normalized regional temperature anomalies versus normalized regional precipitation and subsurface runoff anomalies (for example, see Figure 1) and the results of regression analyses to quantify the relationships between level of stratospheric optical property modification (i.e., geoengineering) and regional hydrology. Results show that while such shortwave compensations for longwave anthropogenic forcings does generally return regional climates to closer to their baseline climate states than the no-geoengineering, business-as-usual scenarios, the magnitudes and sensitivities of regional responses to this type of activity, as modeled in HadCM3L, are highly variable. Regions, such as Eastern China and India, migrate away from their baseline climate states in different ways, illustrating the impossibility of simultaneous stabilization of regional climates. The linearity of the effect of incrementally increasing stratospheric optical depth also varies regionally. Figure 1: Normalized regional temperature and precipitation anomalies (<2020s>-<1990s> and <2070s>-<1990s>) in units of baseline standard deviations for each region). Each grayscale point in-series near the origin

  16. Cultural accommodation of the Strengthening Families Programme 10-14: UK Phase I study.

    PubMed

    Allen, Debby; Coombes, Lindsey; Foxcroft, David R

    2007-08-01

    Social and cultural differences between the United States and the United Kingdom mean that positive results from US prevention programmes may not translate to the United Kingdom. The Strengthening Families Programme 10-14 (SFP10-14) has been evaluated in a large Phase III randomized controlled trial in rural Iowa in the United States and shown to be effective for delaying alcohol and drug initiation. This paper reports the first stage of the adaptation and evaluation of the SFP10-14 for the United Kingdom through a process of cultural accommodation of the SFP10-14 materials and format. Themes that emerged in nominal group and focus group research with young people and their parents indicated that changes to the US SFP10-14 materials needed to consider language, narrators, realism, acceptability of exercises/games, perceived religiosity and ethnic representativeness. However, not all changes reflected straightforward cultural differences, as adaptations were also required to improve the quality and to update the material, indicating that cultural accommodation does not necessarily imply cultural diversity. PMID:17041022

  17. Stable relativistic/charge-displacement channels in ultrahigh power density (≈1021 W/cm3) plasmas

    PubMed Central

    Borisov, A. B.; Longworth, J. W.; Boyer, K.; Rhodes, C. K.

    1998-01-01

    Robust stability is a chief characteristic of relativistic/charge-displacement self-channeling. Theoretical analysis of the dynamics of this stability (i) reveals a leading role for the eigenmodes in the development of stable channels, (ii) suggests a technique using a simple longitudinal gradient in the electron density to extend the zone of stability into the high electron density/high power density regime, (iii) indicates that a situation approaching unconditional stability can be achieved, (iv) demonstrates the efficacy of the stable dynamics in trapping severely perturbed beams in single uniform channels, and (v) predicts that ≈104 critical powers can be trapped in a single stable channel. The scaling of the maximum power density with the propagating wavelength λ is shown to be proportional to λ−4 for a given propagating power and a fixed ratio of the electron plasma density to the critical plasma density. An estimate of the maximum power density that can be achieved in these channels with a power of ≈2 TW at a UV (248 nm) wavelength gives a value of ≈1021 W/cm3 with a corresponding atomic specific magnitude of ≈60 W/atom. The characteristic intensity propagating in the channel under these conditions exceeds 1021 W/cm2. PMID:9653104

  18. Gas- and particle-phase distribution of polycyclic aromatic hydrocarbons in two-stroke, 50-cm 3 moped emissions

    NASA Astrophysics Data System (ADS)

    Spezzano, Pasquale; Picini, Paolo; Cataldi, Dario

    Gas- and particle-phase polycyclic aromatic hydrocarbons (PAHs) concentrations evaluated in the exhaust of 10 two-stroke, 50-cm 3 mopeds belonging to three different levels of emission legislation (EURO-0, EURO-1 and EURO-2) were used to assess the prevalent mechanism driving the gas/particle partitioning of PAHs in moped exhaust. Sampling was performed on a dynamometer bench both during the "cold-start" and the "hot" phases of the ECE-47 driving cycle. Gas and particulate phase PAHs were collected on polyurethane foam (PUF) plugs and 47-mm Pallflex T60A20 filters, respectively, under isokinetic conditions by using sampling probes inserted into the dilution tunnel of a Constant Volume Sampling - Critical Flow Venturi (CVS-CFV) system. The results show that semi-volatile PAHs were predominantly partitioned to the particle phase. The soluble organic fraction (SOF) of the collected particulates ranged between 72 and 98%. Measured total suspended particulate matter normalized partition coefficients ( Kp) were predicted within a factor of 3-5 by assuming absorption into the organic fraction according to a model developed by Harner and Bidleman [Harner, T., Bidleman, T.F., 1998. Octanol-air partition coefficient for describing particle/gas partitioning of aromatic compounds in urban air. Environmental Science & Technology 32, 1494-1502.]. This suggests that the gas/particle partitioning in moped exhaust is mainly driven by the high fraction of organic matter of the emitted particles and that absorption could be the main partitioning mechanism of PAHs.

  19. Particle- and gas-phase emissions of polycyclic aromatic hydrocarbons from two-stroke, 50-cm 3 mopeds

    NASA Astrophysics Data System (ADS)

    Spezzano, Pasquale; Picini, Paolo; Cataldi, Dario; Messale, Fabrizio; Manni, Claudio

    2008-06-01

    The emissions of gas- and particle-phase polycyclic aromatic hydrocarbons (PAHs) were evaluated in the exhaust of 10 mopeds (4 EURO-0, 4 EURO-1 and 2 EURO-2) equipped with two-stroke engines with displacement of 50 cm3. Sampling was performed on a dynamometer bench both during the "cold-start" and the "hot" phases of the ECE-47 driving cycle. Eighteen PAHs were quantified and total PAH emission factors (∑PAH) ranged from 1790 to 15,059 μg km-1. Expressed in benzo(a)pyrene equivalent (BaPeq), emission factors ranged 4.7-86.3 μg km-1. PAH emissions are reduced according to the legislation class: EURO-0>EURO-1>EURO-2. PAH emission factors were greater during the cold-start phase than the hot phase of the ECE-47 cycle. Results show that despite their small engine size, two-stroke mopeds can emit amounts of particulate PAHs comparable or even higher than PAH emissions reported elsewhere from gasoline- and diesel-powered passenger cars and light- and heavy-duty vehicles.

  20. The eastern Tropical Pacific hydroclimate over the last 120kyr: a perspective from HadCM3.

    NASA Astrophysics Data System (ADS)

    Roberts, W. H. G.; Valdes, P. J.

    2014-12-01

    The focus of the majority of studies looking into the evolving tropical pacific climate on glacial/interglacial timescales has been the role of the changing orbital forcing. While this is of course the fundamental forcing that drives changes in the climate on these time scales, without a fully interactive Earth System Model the effects that the evolving ice sheets/sea level and green house gases have on the climate will be missed. In the absence of such models these other forcings must be imposed. While the impact on the temperature in both the high latitudes, and to some extent in the tropics, of all of the forcings is reasonably clear, their impact on the hydroclimate is less obvious. In this study we shall investigate what role all of the different forcings that vary over a glacial/interglacial cycle play on the hydroclimate in the eastern Tropical Pacific. We use as the basis of our study a set of three climate model experiments using the model HadCM3. Each of these simulates the last 120 thousand years as a series of time slices in one of three configurations: varying the orbital forcing; varying the orbital and greenhouse gas forcing; varying the orbital, greenhouse and ice sheet/sea level forcing. With these experiments we can deconvolve the role that each forcing plays. We will show that, in addition to the orbital forcing, both the greenhouse gas forcing and the ice sheet configuration have a large impact on the eastern Tropical Pacific's hydroclimate. Using a set of more idealised model simulations we shall elucidate the mechanisms by which each of these different forcing mechanism causes the simulated changes.

  1. Coupling of a regional atmospheric model (RegCM3) and a regional oceanic model (FVCOM) over the maritime continent

    NASA Astrophysics Data System (ADS)

    Wei, Jun; Malanotte-Rizzoli, Paola; Eltahir, Elfatih A. B.; Xue, Pengfei; Xu, Danya

    2014-09-01

    Climatological high resolution coupled climate model simulations for the maritime continent have been carried out using the regional climate model (RegCM) version 3 and the finite volume coastal ocean model (FVCOM) specifically designed to resolve regions characterized by complex geometry and bathymetry. The RegCM3 boundary forcing is provided by the EMCWF-ERA40 re-analysis. FVCOM is embedded in the Global MITgcm which provides boundary forcing. The domain of the coupled regional model covers the entire South China Sea with its through-flow, the entire Indonesian archipelago with the Indonesian through-flow (ITF) and includes a large region in the western Pacific and eastern Indian oceans. The coupled model is able to provide stable and realistic climatological simulations for a specific decade of atmospheric-oceanic variables without flux correction. The major focus of this work is on oceanic properties. First, the coupled simulation is assessed against ocean-only simulations carried out under two different sets of air-sea heat fluxes. The first set, provided by the MITgcm, is proved to be grossly deficient as the heat fluxes are evaluated by a two-dimensional, zonally averaged atmosphere and the simulated SST have anomalous cold biases. Hence the MITgcm fluxes are discarded. The second set, the NCEP re-analysis heat fluxes, produces a climatological evolution of the SST with an average cold bias of ~-0.8 °C. The coupling eliminates the cold bias and the coupled SST evolution is in excellent agreement with the analogous evolution in the SODA re-analysis data. The detailed comparison of oceanic circulation properties with the International Nusantara Stratification and Transport observations shows that the coupled simulation produces the best estimate of the total ITF transport through the Makassar strait while the transports of three ocean-only simulations are all underestimated. The annual cycle of the transport is also very well reproduced. The coupling also

  2. Very high (> 1019 cm-3) in situ n-type doping of silicon during molecular beam epitaxy using supersonic jets of phosphine

    NASA Astrophysics Data System (ADS)

    Malik, R.; Gulari, E.; Bhattacharya, P.; Linder, K. K.; Rieh, J.-S.

    1997-03-01

    The use of supersonically injected pulses of phosphine to achieve uniform and high levels of n-type doping in Si during gas-source molecular beam epitaxy is demonstrated. Uniform n-type doping up to levels of 5×1019 cm-3 is obtained. SiGe/Si junction diodes made with this doping technique show good doping profiles and rectifying characteristics.

  3. Analysis of the present and future winter Pacific-North American teleconnection in the ECHAM5 global and RegCM3 regional climate models

    USGS Publications Warehouse

    Allan, Andrea M.; Hostetler, Steven W.; Alder, Jay R.

    2014-01-01

    We use the NCEP/NCAR Reanalysis (NCEP) and the MPI/ECHAM5 general circulation model to drive the RegCM3 regional climate model to assess the ability of the models to reproduce the spatiotemporal aspects of the Pacific-North American teleconnection (PNA) pattern. Composite anomalies of the NCEP-driven RegCM3 simulations for 1982–2000 indicate that the regional model is capable of accurately simulating the key features (500-hPa heights, surface temperature, and precipitation) of the positive and negative phases of the PNA with little loss of information in the downscaling process. The basic structure of the PNA is captured in both the ECHAM5 global and ECHAM5-driven RegCM3 simulations. The 1950–2000 ECHAM5 simulation displays similar temporal and spatial variability in the PNA index as that of NCEP; however, the magnitudes of the positive and negative phases are weaker than those of NCEP. The RegCM3 simulations clearly differentiate the climatology and associated anomalies of snow water equivalent and soil moisture of the positive and negative PNA phases. In the RegCM3 simulations of the future (2050–2100), changes in the location and extent of the Aleutian low and the continental high over North America alter the dominant flow patterns associated with positive and negative PNA modes. The future projections display a shift in the patterns of the relationship between the PNA and surface climate variables, which suggest the potential for changes in the PNA-related surface hydrology of North America.

  4. Strengthening families program (10-14): effects on the family environment.

    PubMed

    Riesch, Susan K; Brown, Roger L; Anderson, Lori S; Wang, Kevin; Canty-Mitchell, Janie; Johnson, Deborah L

    2012-04-01

    This study examined whether parent-youth dyads participating in the Strengthening Families Program 10-14 (SFP 10-14) would demonstrate greater postprogram family cohesion, communication, involvement, and supervision and if youth would report less alcohol, tobacco, and other drugs involvement in contrast to a comparison group. From 16 randomly selected schools, we recruited 167 parent-youth dyads: 86 from intervention and 81 from comparison schools. The intention-to-treat analysis found one significant change in family environment. Considering dose, it was found that among dyads receiving a full dose, all the outcomes were in the expected direction and effect sizes were moderate. Among dyads receiving a partial dose, 10 of 18 outcomes were in the direction opposite that expected. Youth participation in alcohol, tobacco, and other drugs was very low and did not differ postprogram. Although the expected outcomes were not realized, findings descriptive of dosage effects make a valuable contribution to the field. Study of factors that distinguish intervention completers from noncompleters is recommended. PMID:21403057

  5. Newly Installed S-1 Truss

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Launched October 7, 2002 aboard the Space Shuttle Orbiter Atlantis, the STS-112 mission lasted 11 days and performed three sessions of Extra Vehicular Activity (EVA). Its primary mission was to install the Starboard (S1) Integrated Truss Structure and Equipment Translation Aid (CETA) Cart to the International Space Station (ISS). The S1 truss provides structural support for the orbiting research facility's radiator panels, which use ammonia to cool the Station's complex power system. The S1 truss, attached to the S0 (S Zero) truss installed by the previous STS-110 mission, flows 637 pounds of anhydrous ammonia through three heat rejection radiators. The truss is 45-feet long, 15-feet wide, 10-feet tall, and weighs approximately 32,000 pounds. The CETA is the first of two human-powered carts that will ride along the International Space Station's railway providing a mobile work platform for future extravehicular activities by astronauts. This is a view of the newly installed S1 Truss as photographed during the mission's first scheduled EVA. The Station's Canadarm2 is in the foreground. Visible are astronauts Piers J. Sellers (lower left) and David A. Wolf (upper right), both STS-112 mission specialists.

  6. Impact of resolution on regional climate modeling in the source region of Yellow River with complex terrain using RegCM3

    NASA Astrophysics Data System (ADS)

    Hui, Pinhong; Tang, Jianping; Wang, Shuyu; Wu, Jian; Niu, Xiaorui; Kang, Yue

    2015-05-01

    This paper presents results from a 20-year (1990-2009) simulation by RegCM3 with both 45- and 15-km horizontal resolutions. The research focuses on the source region of Yellow River and its surrounding area, which is located on the northeast edge of the Tibetan Plateau with its very complex topography. Driven by the ECMWF ERA-interim reanalysis data, RegCM3 displays reasonable ability to reproduce the spatial patterns, annual cycles, and the interannual variabilities of regional surface climate, though the model shows wet and cold bias. The model's performance is more close to observation for the source region of Yellow River than the other part of the analysis region, and the application of high resolution of 15 km demonstrates better skill with less bias for mean climate and larger correlation coefficients for interannual variability at most stations. However, the high-resolution simulation shows little advantage for reproducing the variations of precipitation and surface air temperature with altitude. The RegCM3 model also generally reproduces the probability distribution functions (PDFs) of surface climate and, consequently, the occurrence of climatic extremes and extreme indices. The simulation with high resolution again proves to be more reliable to generate climatic extremes over complex terrain of the source region of the Yellow River, related to its better representation of complex terrain and local processes.

  7. Impact of resolution on regional climate modeling in the source region of Yellow River with complex terrain using RegCM3

    NASA Astrophysics Data System (ADS)

    Hui, Pinhong; Tang, Jianping; Wang, Shuyu; Wu, Jian; Niu, Xiaorui; Kang, Yue

    2016-07-01

    This paper presents results from a 20-year (1990-2009) simulation by RegCM3 with both 45- and 15-km horizontal resolutions. The research focuses on the source region of Yellow River and its surrounding area, which is located on the northeast edge of the Tibetan Plateau with its very complex topography. Driven by the ECMWF ERA-interim reanalysis data, RegCM3 displays reasonable ability to reproduce the spatial patterns, annual cycles, and the interannual variabilities of regional surface climate, though the model shows wet and cold bias. The model's performance is more close to observation for the source region of Yellow River than the other part of the analysis region, and the application of high resolution of 15 km demonstrates better skill with less bias for mean climate and larger correlation coefficients for interannual variability at most stations. However, the high-resolution simulation shows little advantage for reproducing the variations of precipitation and surface air temperature with altitude. The RegCM3 model also generally reproduces the probability distribution functions (PDFs) of surface climate and, consequently, the occurrence of climatic extremes and extreme indices. The simulation with high resolution again proves to be more reliable to generate climatic extremes over complex terrain of the source region of the Yellow River, related to its better representation of complex terrain and local processes.

  8. The dynamical core, physical parameterizations, and basic simulation characteristics of the atmospheric component AM3 of the GFDL global coupled model CM3

    USGS Publications Warehouse

    Donner, L.J.; Wyman, B.L.; Hemler, R.S.; Horowitz, L.W.; Ming, Y.; Zhao, M.; Golaz, J.-C.; Ginoux, P.; Lin, S.-J.; Schwarzkopf, M.D.; Austin, J.; Alaka, G.; Cooke, W.F.; Delworth, T.L.; Freidenreich, S.M.; Gordon, C.T.; Griffies, S.M.; Held, I.M.; Hurlin, W.J.; Klein, S.A.; Knutson, T.R.; Langenhorst, A.R.; Lee, H.-C.; Lin, Y.; Magi, B.I.; Malyshev, S.L.; Milly, P.C.D.; Naik, V.; Nath, M.J.; Pincus, R.; Ploshay, J.J.; Ramaswamy, V.; Seman, C.J.; Shevliakova, E.; Sirutis, J.J.; Stern, W.F.; Stouffer, R.J.; Wilson, R.J.; Winton, M.; Wittenberg, A.T.; Zeng, F.

    2011-01-01

    The Geophysical Fluid Dynamics Laboratory (GFDL) has developed a coupled general circulation model (CM3) for the atmosphere, oceans, land, and sea ice. The goal of CM3 is to address emerging issues in climate change, including aerosol-cloud interactions, chemistry-climate interactions, and coupling between the troposphere and stratosphere. The model is also designed to serve as the physical system component of earth system models and models for decadal prediction in the near-term future-for example, through improved simulations in tropical land precipitation relative to earlier-generation GFDL models. This paper describes the dynamical core, physical parameterizations, and basic simulation characteristics of the atmospheric component (AM3) of this model. Relative to GFDL AM2, AM3 includes new treatments of deep and shallow cumulus convection, cloud droplet activation by aerosols, subgrid variability of stratiform vertical velocities for droplet activation, and atmospheric chemistry driven by emissions with advective, convective, and turbulent transport. AM3 employs a cubed-sphere implementation of a finite-volume dynamical core and is coupled to LM3, a new land model with ecosystem dynamics and hydrology. Its horizontal resolution is approximately 200 km, and its vertical resolution ranges approximately from 70 m near the earth's surface to 1 to 1.5 km near the tropopause and 3 to 4 km in much of the stratosphere. Most basic circulation features in AM3 are simulated as realistically, or more so, as in AM2. In particular, dry biases have been reduced over South America. In coupled mode, the simulation of Arctic sea ice concentration has improved. AM3 aerosol optical depths, scattering properties, and surface clear-sky downward shortwave radiation are more realistic than in AM2. The simulation of marine stratocumulus decks remains problematic, as in AM2. The most intense 0.2% of precipitation rates occur less frequently in AM3 than observed. The last two decades of

  9. Climate Impact on South America due to Land Use Degradation of Amazon Rainforest during Winter and Summer Periods by RegCM3 Model

    NASA Astrophysics Data System (ADS)

    Silva, M. E. S.; Da Rocha, R.; Pereira, G.

    2015-12-01

    In this study we investigated the climatic impact over South America region due to the increasing of deforestation at the eastern and southern regions of Amazon through the use of the climate model RegCM3 with 50 km of spatial resolution. Many studies, among global and regional models have been used to simulate climatic impact due to deforestation. Most of them used relatively coarse resolution, small domains over South America, besides do not consider deforestation as usually observed. In order to verify the RegCM3 ability to simulate climate impacts due to Amazon deforestation including relatively higher horizontal resolutions, 50 km, a larger domain, the whole South America, deforested areas more similar to the route-shaped commonly seen, and a landuse updating, the model was run for the 2001-2006 period. As the major part of the previous studies focusing Amazon deforestation, RegCM3-50km simulated over degraded areas air temperature increase, ranging from 1.0 to 2.5oC, and precipitation decreasing, ~10%. These aspects are mainly resulting from soil water depletion and roughness vegetation decreasing, both inhibiting evapotranspiration processes. Apart from these results, the model with 50 km simulated precipitation increasing, ~10%, over the eastern South America and adjacent South Atlantic ocean, after Amazon deforestation. Seeking for physical related reasons able to provide the precipitation increasing during rainy seasons, over eastern South America, we found out that upper levels high pressure system (the Bolivian High) intensification, coupled to the southeastward trough, what follows the low troposphere warming, seems to contribute to the precipitation increasing. The climatic impact simulated for winter seasons presents strongest values for areas with altered landuse, over the north region of South America.

  10. Disposition of the plasmacytomagenic alkane pristane (2,6,10,14-tetramethylpentadecane) in mice.

    PubMed

    Janz, S; Shacter, E

    1995-06-01

    The intraperitoneal administration of pristane (2,6,10,14-tetramethylpentadecane) induces peritoneal plasmacytomas in genetically susceptible BALB/c mice. The purpose of this study was to estimate the disposition of an amount of intraperitoneally injected pristane that would conventionally be used in a tumor induction protocol. The distribution of 3H-labeled pristane in various tissues was monitored by liquid scintillation counting at different times after injection. The data show that pristane is present in the blood and detectable in all tested tissues during an observation period of one to 64 days. The levels of pristane fluctuate in some tissues such as lymph node and bone marrow but show a clear tendency to accumulate in others such as liver, spleen and kidney. Evidence is also presented for the in vivo metabolism of pristane based on the observed urinary excretion of tritium and on the high levels of radioactivity in the gall bladder fluid. It is concluded that intraperitoneally administered pristane is distributed throughout the mouse and is stored in tissues in sufficient amounts to allow interactions with the cells residing there. PMID:8536217

  11. American Fisheries Society 136th Annual Meeting Lake Placid, NY 10-14 September, 2006

    USGS Publications Warehouse

    Einhouse, D.; Walsh, M.G.; Keeler, S.; Long, J.M.

    2005-01-01

    The New York Chapter of the American Fisheries Society and the New York State Department of Environmental Conservation invite you to experience the beauty of New York's famous Adirondack Park as the American Fisheries Society (AFS) convenes its 136th Annual Meeting in the legendary Olympic Village of Lake Placid, NY, 10-14 September 2006. Our meeting theme "Fish in the Balance" will explore the interrelation between fish, aquatic habitats, and man, highlighting the challenges facing aquatic resource professionals and the methods that have been employed to resolve conflicts between those that use or have an interest in our aquatic resources. As fragile as it is beautiful, the Adirondack Region is the perfect location to explore this theme. Bordered by Mirror Lake and its namesake, Lake Placid, the Village of Lake Placid has small town charm, but all of the conveniences that a big city would provide. Whether its reliving the magic of the 1980 hockey team's "Miracle on Ice" at the Lake Placid Olympic Center, getting a panoramic view of the Adirondack high peaks from the top of the 90 meter ski jumps, fishing or kayaking in adjacent Mirror Lake, hiking a mountain trail, or enjoying a quiet dinner or shopping excursion in the various shops and restaurants that line Main Street, Lake Placid has something for everyone.

  12. Single Fetal Demise at 10 - 14 Weeks of Monochorionic and Dichorionic Twin Pregnancy

    PubMed Central

    Suzuki, Shunji

    2016-01-01

    Background We examined the perinatal outcomes in cases of at least one fetal demise in monochorionic and diamniotic twin pregnancies. Methods We reviewed the obstetric records of all Japanese twin pregnancies managed beyond 9 weeks’ gestation at Japanese Red Cross Katsushika Maternity Hospital between 2008 and 2014. Results The incidence in the monochorionic twin pregnancies was significantly higher than that in the dichorionic twin pregnancies (8.3% vs. 2.6%, odds ratio: 3.40, 95% confidence interval: 1.5 - 7.6, P < 0.01). Of these, 60.0% were diagnosed as fetal demise of both fetuses at the same time (vs. dichorionic twin pregnancy: odds ratio: 12.0, 95% confidence interval: 1.3 - 120, P = 0.04). The rate of “vanishing twin” in cases of at least one fetal demise at 10 - 14 weeks’ gestation in the monochorionic twin pregnancies was significantly lower than that in the diamniotic twin pregnancies (30.0% vs. 88.9%, odds ratio: 0.05, 95% confidence interval: 0.01 - 0.53, P = 0.01). Conclusion The incidence of fetal demise and the influence on the co-twin in monochorionic twin pregnancy is greater than those in dichorionic twin pregnancy. PMID:26985254

  13. Speculations on a relativistic strong focusing self-collider with very high luminosity (≥10 40 cm -2s -1): Macroproduction of antinuclei and other micro cross section events and formation of ambiplasma

    NASA Astrophysics Data System (ADS)

    Maglich, Bogdan C.

    1988-08-01

    The luminosity of the weak focusing self-collider (ESCOL) is intrinsically 10 8-10 10 times greater than that of conventional colliding beams, due to the product of the solid angle factor, ˜10 6, and the neutralization factor, ˜10 2 -10 4. We extrapolate to 10-GeV protons the parameters of a recent low energy experiment demonstrating that a 1-MeV deuteron beam, stored in ESCOL as migma, can be neutralized bo oscillating electrons and operate an order of magnitude above the space charge limit without instabilities. With the number density achieved in ESCOL, n = 3.2 × 10 9 ions cm -3, such a relativistic strong focusing self-collider (XYDER) would have a luminosity L ˜ 10 38 cm -2 s -1 for 10-GeV-on-10-GeV protons (equivalent to 250 GeV beam-on-target). At the diamagnetic "limit" density, which for 10 tesla is n = 10 12 ions cm -3, l ˜ 10 43 cm -2 s -1; this would produce 4 × 10 16 antiprotons/s (2 gram of overlinep/year). Other particles, rare nuclei, and rare effects produced with micro- (10 -16), nano- (10 -9 b), and picoscopic (10 -12 b) cross sections will be macro-produced in XYDER. A newly proposed annular magnet would provide a large volume of stored, V = 10 9 cm 3, as well as automatic ejection along the +z and -z axes of the overlinep's and other particles whose momentum is lower than that of the primary proton migma. Antiprotons, being produced with low rapidity, will have energies below 1 GeV in COM, and thus are suitable for beaming, extraction, cooling, abd slowing down to be either stored for space propulsion or used as a source for acceleration. If the magnetic field strength is adjusted for the antiprotons to be confined, an unusual plasma will be formed, consisting of the protons, antiprotons, electrons, and positrons (from pion-muon-electron decays), and similar to Alfvèns "ambiplasman". Its plasmic beta will be unity already at low densities (˜10 11 cm -3 where ωpi/ ωci ≤ 1); the ion-to-electron "temperature" ratio will never achieve

  14. Accurate quantum chemical modelling of the separation of Eu(3+) from Am(3+)/Cm(3+) by liquid-liquid extraction with Cyanex272.

    PubMed

    Cao, Xiaoyan; Zhang, Jun; Weissmann, Daniel; Dolg, Michael; Chen, Xuebo

    2015-08-28

    The experimentally observed extraction complexes of trivalent lanthanide Eu(3+) and actinide Am(3+)/Cm(3+) cations with Cyanex272 [bis(2,4,4-trimethylpentyl) phosphinic acid, denoted as HC272] and Cyanex301 [bis(2,4,4-trimethylpentyl) dithiophosphinic acid, denoted as HC301] have been studied by using relativistic energy-consistent 4f- and 5f-in-core pseudopotentials for trivalent f elements, combined with density functional theory and a continuum solvation model. It has been found that, as a result of hydrogen bonding, HC272 exists primarily as a self-associated species, whereas HC301 is preferably a monomer. The calculations show that in case of all three M(3+) (M = Eu, Am, Cm) ions for HC272 the extraction complexes M[H(C272)2]3 are formed prior to M(C272)3, whereas for HC301 the extraction complexes M(C301)3 have priority over M[H(C301)2]3. The calculated M-O and M-S bond lengths and the M-P distances of these preferred extraction complexes agree very well with the available experimental data. The obtained changes of the Gibbs free energies in the liquid-liquid extraction reactions (1): Maqu(3+) + 3(HC272)2,org→ M[H(C272)2]3,org + 3Haqu(+) and (2): Maqu(3+) + 3HC301org→ M(C301)3,org + 3Haqu(+) agree with the experimentally observed thermodynamical priorities of HC272 and HC301, i.e., HC272 prefers Eu(3+) over Am(3+)/Cm(3+) and HC301 prefers Am(3+)/Cm(3+) over Eu(3+). The obtained changes of the Gibbs free energies in reaction (2) (Eu, 68.1 kJ mol(-1); Am, 46.5 kJ mol(-1)) agree quite well with the experimental findings (Eu, 63.3 kJ mol(-1); Am, 44.1 kJ mol(-1)). PMID:26203895

  15. Aerobic and anaerobic metabolism of 6,10,14-trimethylpentadecan-2-one by a denitrifying bacterium isolated from marine sediments.

    PubMed Central

    Rontani, J F; Gilewicz, M J; Michotey, V D; Zheng, T L; Bonin, P C; Bertrand, J C

    1997-01-01

    This report describes the metabolism of 6,10,14-trimethylpentadecan-2-one by a denitrifying bacterium (Marinobacter sp. strain CAB) isolated from marine sediments. Under aerobic and denitrifying conditions, this strain efficiently degraded this ubiquitous isoprenoid ketone. Several bacterial metabolites, 4,8,12-trimethyl-tridecan-1-ol, 4,8,12-trimethyltridecanal, 4,8,12-trimethyltridecanoic acid, Z-3,7-dimethylocten-2-oic acid, Z-3,7,11-trimethyldodecen-2-oic acid, and 6,10,14-trimethylpentadecan-2-ol, were formally identified, and different pathways were proposed to explain the formation of such isoprenoid compounds. PMID:9023941

  16. Parameter Tuning and Calibration of RegCM3 with MIT-Emanuel Cumulus Parameterization Scheme over CORDEX East Asian Domain

    SciTech Connect

    Zou, Liwei; Qian, Yun; Zhou, Tianjun; Yang, Ben

    2014-10-01

    In this study, we calibrated the performance of regional climate model RegCM3 with Massachusetts Institute of Technology (MIT)-Emanuel cumulus parameterization scheme over CORDEX East Asia domain by tuning the selected seven parameters through multiple very fast simulated annealing (MVFSA) sampling method. The seven parameters were selected based on previous studies, which customized the RegCM3 with MIT-Emanuel scheme through three different ways by using the sensitivity experiments. The responses of model results to the seven parameters were investigated. Since the monthly total rainfall is constrained, the simulated spatial pattern of rainfall and the probability density function (PDF) distribution of daily rainfall rates are significantly improved in the optimal simulation. Sensitivity analysis suggest that the parameter “relative humidity criteria” (RH), which has not been considered in the default simulation, has the largest effect on the model results. The responses of total rainfall over different regions to RH were examined. Positive responses of total rainfall to RH are found over northern equatorial western Pacific, which are contributed by the positive responses of explicit rainfall. Followed by an increase of RH, the increases of the low-level convergence and the associated increases in cloud water favor the increase of the explicit rainfall. The identified optimal parameters constrained by the total rainfall have positive effects on the low-level circulation and the surface air temperature. Furthermore, the optimized parameters based on the extreme case are suitable for a normal case and the model’s new version with mixed convection scheme.

  17. IUTAM Symposium on Vortex Dynamics: Formation, Structure and Function, 10-14 March 2013, Fukuoka, Japan

    NASA Astrophysics Data System (ADS)

    Fukumoto, Yasuhide

    2014-06-01

    This special issue of Fluid Dynamics Research contains the first of a two-part publication of the papers presented at the IUTAM Symposium on Vortex Dynamics: Formation, Structure and Function, held at the Centennial Hall, Kyushu University School of Medicine, Fukuoka, Japan, during the week of 10-14 March 2013. Vortices are ubiquitous structures in fluid mechanics spanning the range of scales from nanofluidics and microfluidics to geophysical and astrophysical flows. Vortices are the key to understanding many different phenomena. As a result, the subject of vortex dynamics continues to evolve and to constantly find new applications in biology, biotechnology, industrial and environmental problems. Vortices can be created by the separation of a flow from the surface of a body or at a density interface, and evolve into coherent structures. Once formed, a vortex acquires a function, depending on its individual structure. In this way, for example, insects gain lift and fish gain thrust. Surprisingly, despite the long history of vortex dynamics, only recently has knowledge about formation, structure and function of vortices been combined to yield new perspectives in the subject, thereby helping to solve outstanding problems brought about by modern advances in computer technology and improved experimental techniques. This symposium is a continuation, five years on, of the IUTAM Symposium '50 Years of Vortex Dynamics', Lyngby, Denmark that took place between 12-16 October 2008, organized by the late Professor Hassan Aref. Originally, Professor Aref was a member of the International Scientific Committee of this symposium and offered his enthusiasm and great expertise, to support its organization. To our shock, he suddenly passed away on 9 September 2011. Furthermore, Professor Slava Meleshko, a leading scientist of fluid and solid mechanics and an intimate friend of Professor Aref, was expected to make an eminent contribution to the symposium. Soon after this sad loss

  18. Silicon photomultiplier readout of a monolithic 270×5×5 cm3 plastic scintillator bar for time of flight applications

    NASA Astrophysics Data System (ADS)

    Reinhardt, Tobias P.; Gohl, Stefan; Reinicke, Stefan; Bemmerer, Daniel; Cowan, Thomas E.; Heidel, Klaus; Röder, Marko; Stach, Daniel; Wagner, Andreas; Weinberger, David; Zuber, Kai

    2016-04-01

    The detection of 200-1000 MeV neutrons requires large amounts, ~ 100 cm, of detector material because of the long nuclear interaction length of these particles. In the example of the NeuLAND neutron time-of-flight detector at FAIR, this is accomplished by using 3000 monolithic scintillator bars of 270 × 5 × 5cm3 size made of a fast plastic. Each bar is read out on the two long ends, and the needed time resolution of σt < 150 ps is reached with fast timing photomultipliers. In the present work, it is investigated whether silicon photomultiplier (SiPM) photosensors can be used instead. Experiments with a picosecond laser system were conducted to determine the timing response of the assembly made up of SiPM and preamplifier. The response of the full system including also the scintillator was studied using 30 MeV single electrons provided by the ELBE superconducting electron linac. The ELBE data were matched by a simple Monte Carlo simulation, and they were found to obey an inverse-square-root scaling law. In the electron beam tests, a time resolution of σt = 136 ps was reached with a pure SiPM readout, well within the design parameters for NeuLAND.

  19. Monte Carlo correction factors for a Farmer 0.6 cm3 ion chamber dose measurement in the build-up region of the 6 MV clinical beam.

    PubMed

    Pena, J; Sánchez-Doblado, F; Capote, R; Terrón, J A; Gómez, F

    2006-03-21

    Reference dosimetry of photon fields is a well-established subject and currently available protocols (such as the IAEA TRS-398 and AAPM TG-51) provide methods for converting the ionization chamber (IC) reading into dose to water, provided reference conditions of charged particle equilibrium (CPE) are fulfilled. But these protocols cannot deal with the build-up region, where the lack of CPE limits the applicability of the cavity theorems and so the chamber correction factors become depth dependent. By explicitly including the IC geometry in the Monte Carlo simulations, depth-dependent dose correction factors are calculated for a PTW 30001 0.6 cm(3) ion chamber in the build-up region of the 6 MV photon beam. The corrected percentage depth dose (PDD) agrees within 2% with that measured using the NACP 02 plane-parallel ion chamber in the build-up region at depths greater than 0.4 cm, where the Farmer chamber wall reaches the phantom surface. PMID:16510960

  20. IUTAM Symposium on Vortex Dynamics: Formation, Structure and Function, 10-14 March 2013, Fukuoka, Japan

    NASA Astrophysics Data System (ADS)

    Fukumoto, Yasuhide

    2014-06-01

    This special issue of Fluid Dynamics Research contains the first of a two-part publication of the papers presented at the IUTAM Symposium on Vortex Dynamics: Formation, Structure and Function, held at the Centennial Hall, Kyushu University School of Medicine, Fukuoka, Japan, during the week of 10-14 March 2013. Vortices are ubiquitous structures in fluid mechanics spanning the range of scales from nanofluidics and microfluidics to geophysical and astrophysical flows. Vortices are the key to understanding many different phenomena. As a result, the subject of vortex dynamics continues to evolve and to constantly find new applications in biology, biotechnology, industrial and environmental problems. Vortices can be created by the separation of a flow from the surface of a body or at a density interface, and evolve into coherent structures. Once formed, a vortex acquires a function, depending on its individual structure. In this way, for example, insects gain lift and fish gain thrust. Surprisingly, despite the long history of vortex dynamics, only recently has knowledge about formation, structure and function of vortices been combined to yield new perspectives in the subject, thereby helping to solve outstanding problems brought about by modern advances in computer technology and improved experimental techniques. This symposium is a continuation, five years on, of the IUTAM Symposium '50 Years of Vortex Dynamics', Lyngby, Denmark that took place between 12-16 October 2008, organized by the late Professor Hassan Aref. Originally, Professor Aref was a member of the International Scientific Committee of this symposium and offered his enthusiasm and great expertise, to support its organization. To our shock, he suddenly passed away on 9 September 2011. Furthermore, Professor Slava Meleshko, a leading scientist of fluid and solid mechanics and an intimate friend of Professor Aref, was expected to make an eminent contribution to the symposium. Soon after this sad loss

  1. Sensitivity studies of high-resolution RegCM3 simulations of precipitation over the European Alps: the effect of lateral boundary conditions and domain size

    NASA Astrophysics Data System (ADS)

    Nadeem, Imran; Formayer, Herbert

    2015-08-01

    A suite of high-resolution (10 km) simulations were performed with the International Centre for Theoretical Physics (ICTP) Regional Climate Model (RegCM3) to study the effect of various lateral boundary conditions (LBCs), domain size, and intermediate domains on simulated precipitation over the Great Alpine Region. The boundary conditions used were ECMWF ERA-Interim Reanalysis with grid spacing 0.75∘, the ECMWF ERA-40 Reanalysis with grid spacing 1.125 and 2.5∘, and finally the 2.5∘ NCEP/DOE AMIP-II Reanalysis. The model was run in one-way nesting mode with direct nesting of the high-resolution RCM (horizontal grid spacing Δx = 10 km) with driving reanalysis, with one intermediate resolution nest (Δx = 30 km) between high-resolution RCM and reanalysis forcings, and also with two intermediate resolution nests (Δx = 90 km and Δx = 30 km) for simulations forced with LBC of resolution 2.5∘. Additionally, the impact of domain size was investigated. The results of multiple simulations were evaluated using different analysis techniques, e.g., Taylor diagram and a newly defined useful statistical parameter, called Skill-Score, for evaluation of daily precipitation simulated by the model. It has been found that domain size has the major impact on the results, while different resolution and versions of LBCs, e.g., 1.125∘ ERA40 and 0.7∘ ERA-Interim, do not produce significantly different results. It is also noticed that direct nesting with reasonable domain size, seems to be the most adequate method for reproducing precipitation over complex terrain, while introducing intermediate resolution nests seems to deteriorate the results.

  2. CYP2S1: A short review

    SciTech Connect

    Saarikoski, Sirkku T. . E-mail: sirkku.saarikoski@ktl.fi; Rivera, Steven P.; Hankinson, Oliver; Husgafvel-Pursiainen, Kirsti

    2005-09-01

    A new member of the cytochrome P450 superfamily, CYP2S1, has recently been identified in human and mouse. In this paper, we review the data currently available for CYP2S1. The human CYP2S1 gene is located in chromosome 19q13.2 within a cluster including CYP2 family members CYP2A6, CYP2A13, CYP2B6, and CYP2F1. These genes also show the highest homology to the human CYP2S1. The gene has recently been found to harbor genetic polymorphism. CYP2S1 is inducible by dioxin, the induction being mediated by the Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Nuclear Translocator (ARNT) in a manner typical for CYP1 family members. In line with this, CYP2S1 has been shown to be inducible by coal tar, an abundant source of PAHs, and it was recently reported to metabolize naphthalene. This points to the involvement of CYP2S1 in the metabolism of toxic and carcinogenic compounds, similar to other dioxin-inducible CYPs. CYP2S1 is expressed in epithelial cells of a wide variety of extrahepatic tissues. The highest expression levels have been observed in the epithelial tissues frequently exposed to xenobiotics, e.g., the respiratory, gastrointestinal, and urinary tracts, and in the skin. The observed ubiquitous tissue distribution, as well as the expression of CYP2S1 throughout embryogenesis suggest that CYP2S1 is likely to metabolize important endogenous substrates; thus far, retinoic acid has been identified. In conclusion, CYP2S1 exhibits many features of interest for human health and thus warrants further investigation.

  3. CYP2S1: a short review.

    PubMed

    Saarikoski, Sirkku T; Rivera, Steven P; Hankinson, Oliver; Husgafvel-Pursiainen, Kirsti

    2005-09-01

    A new member of the cytochrome P450 superfamily, CYP2S1, has recently been identified in human and mouse. In this paper, we review the data currently available for CYP2S1. The human CYP2S1 gene is located in chromosome 19q13.2 within a cluster including CYP2 family members CYP2A6, CYP2A13, CYP2B6, and CYP2F1. These genes also show the highest homology to the human CYP2S1. The gene has recently been found to harbor genetic polymorphism. CYP2S1 is inducible by dioxin, the induction being mediated by the Aryl Hydrocarbon Receptor (AHR) and Aryl Hydrocarbon Nuclear Translocator (ARNT) in a manner typical for CYP1 family members. In line with this, CYP2S1 has been shown to be inducible by coal tar, an abundant source of PAHs, and it was recently reported to metabolize naphthalene. This points to the involvement of CYP2S1 in the metabolism of toxic and carcinogenic compounds, similar to other dioxin-inducible CYPs. CYP2S1 is expressed in epithelial cells of a wide variety of extrahepatic tissues. The highest expression levels have been observed in the epithelial tissues frequently exposed to xenobiotics, e.g., the respiratory, gastrointestinal, and urinary tracts, and in the skin. The observed ubiquitous tissue distribution, as well as the expression of CYP2S1 throughout embryogenesis suggest that CYP2S1 is likely to metabolize important endogenous substrates; thus far, retinoic acid has been identified. In conclusion, CYP2S1 exhibits many features of interest for human health and thus warrants further investigation. PMID:16054184

  4. Safety assessment for the S-1 Spheromak

    SciTech Connect

    Ellis, R. Jr.; Stencel, J.R.

    1984-02-01

    The S-1 machine is part of the Magnetic Fusion Program. The goal of the Magnetic Fusion Program is to develop and demonstrate the practical application of fusion. S-1 is an experimental device which will provide an essential link in the research effort aiming at the realization of fusion power.

  5. Hypothalamic S1P/S1PR1 axis controls energy homeostasis.

    PubMed

    Silva, Vagner R R; Micheletti, Thayana O; Pimentel, Gustavo D; Katashima, Carlos K; Lenhare, Luciene; Morari, Joseane; Mendes, Maria Carolina S; Razolli, Daniela S; Rocha, Guilherme Z; de Souza, Claudio T; Ryu, Dongryeol; Prada, Patrícia O; Velloso, Lício A; Carvalheira, José B C; Pauli, José Rodrigo; Cintra, Dennys E; Ropelle, Eduardo R

    2014-01-01

    Sphingosine 1-phosphate receptor 1 (S1PR1) is a G-protein-coupled receptor for sphingosine-1-phosphate (S1P) that has a role in many physiological and pathophysiological processes. Here we show that the S1P/S1PR1 signalling pathway in hypothalamic neurons regulates energy homeostasis in rodents. We demonstrate that S1PR1 protein is highly enriched in hypothalamic POMC neurons of rats. Intracerebroventricular injections of the bioactive lipid, S1P, reduce food consumption and increase rat energy expenditure through persistent activation of STAT3 and the melanocortin system. Similarly, the selective disruption of hypothalamic S1PR1 increases food intake and reduces the respiratory exchange ratio. We further show that STAT3 controls S1PR1 expression in neurons via a positive feedback mechanism. Interestingly, several models of obesity and cancer anorexia display an imbalance of hypothalamic S1P/S1PR1/STAT3 axis, whereas pharmacological intervention ameliorates these phenotypes. Taken together, our data demonstrate that the neuronal S1P/S1PR1/STAT3 signalling axis plays a critical role in the control of energy homeostasis in rats. PMID:25255053

  6. Wackenhut Services, Incorporated: Report from the DOE Voluntary Protection Program onsite review, August 10--14, 1998

    SciTech Connect

    1999-05-01

    This report summarizes the Department of Energy Voluntary Protection Program (DOE-VPP) Review Team`s findings from the five-day onsite evaluation of Wackenhut Services, Inc. (WSI) at Savannah River Site (SRS), conducted August 10-14, 1998. The site was evaluated against the program requirements contained in US Department of Energy Voluntary Protection Program, Part 1: Program Elements to determine its success in implementing the five DOE-VPP tenets. The Team determined that WSI has met in varying degrees, all the tenets of the DOE-VPP. In every case, WSI programs and procedures exceed the level or degree necessary for compliance with existing standards, DOE Orders, and guidelines. In addition, WSI has systematically integrated their occupational safety and health (OSH) program into management and work practices at all levels. WSI`s efforts toward implementing the five major DOE-VPP tenets are summarized.

  7. The Global S$_1$ Ocean Tide

    NASA Technical Reports Server (NTRS)

    Ray, Richard D.; Egbert, G. D.

    2003-01-01

    The small S$_1$ ocean tide is caused primarily by diurnal atmospheric pressure loading. Its excitation is therefore unlike any other diurnal tide. The global character of $S-1$ is here determined by numerical modeling and by analysis of Topex/Poseidon satellite altimeter data. The two approaches yield reasonably consistent results, and large ( $ greater than $l\\cm) amplitudes in several regions are further confirmed by comparison with coastal tide gauges. Notwithstanding their excitation differences, S$-1$ and other diurnal tides are found to share several common features, such as relatively large amplitudes in the Arabian Sea, the Sea of Okhotsk, and the Gulf of Alaska. The most noticeable difference is the lack of an S$-1$ Antarctic Kelvin wave. These similarities and differences can be explained in terms of the coherences between near-diurnal oceanic normal modes and the underlying tidal forcings. While gravitational diurnal tidal forces excite primarily a 28-hour Antarctic-Pacific mode, the S$_1$ air tide excites several other near-diurnal modes, none of which has large amplitudes near Antarctica.

  8. Solubility of chlorargyrite (AgCl(cr./l.)) in water: New experimental data and a predictive model valid for a wide range of temperatures (273-873 K) and water densities (0.01-1 g·cm-3)

    NASA Astrophysics Data System (ADS)

    Akinfiev, Nikolay N.; Zotov, Alexander V.

    2016-04-01

    The solubility of chlorargyrite, AgCl(cr./l.), in pure water at 623, 673 and 753 (±2) K as a function of pressure in a wide range aqueous densities (0.01-0.7 g·cm-3) was determined using various experimental approaches. Combined theoretical quantum chemistry simulations of Ag speciation and structure with a recently developed equation of state (EoS) for aqueous neutral species (Akinfiev and Diamond, 2003) were applied to describe published and newly made AgCl(cr./l.) solubility measurements in water. The use of the employed EoS for AgCl(H2O)(aq) cluster is found out to provide a good description of the whole set of experimental measurements in a wide range of temperatures (273-753 K), water densities (0.01-0.7 g·cm-3), and pressures of 0.1-100 MPa. Also, the proposed AgCl(H2O)(aq) thermodynamic description is proved to be valid for a dense aqueous fluid (0.7-1 g·cm-3) at 273-623 K and saturation water pressure. Although silver obviously shows greater affinity to dense aqueous fluid, AgCl hydration in the vapour phase is demonstrated to be also significant. A model extrapolation to magmatic conditions predicts an appreciable silver content even in low density fluids, thus supporting the hypothesis of metal transport with vapour.

  9. LC/MS analysis of proteolytic peptides in wheat extracts for determining the content of the allergen amylase/trypsin inhibitor CM3: influence of growing area and variety.

    PubMed

    Prandi, Barbara; Faccini, Andrea; Tedeschi, Tullia; Galaverna, Gianni; Sforza, Stefano

    2013-09-01

    Food allergy from wheat is triggered by several protein classes, such as LTPs, ω5-gliadins and α-amylase/trypsin inhibitors. The latter proteins, belonging to the prolamin superfamily, are mostly involved in baker's asthma, a form of occupational allergy in which the sensitization occurs through the respiratory tract. α-Amylase/trypsin inhibitors were also found to be involved in wheat-related atopic dermatitis. In this work, the allergen Tri a 30 (the CM3 α-amylase/trypsin inhibitor) was quantified in durum wheat salt soluble extracts using a peptidomic approach. CM3 protein identification was confirmed by using LTQ-OrbiTrap analysis on peptides obtained from the enzymatically digested protein separated by gel electrophoresis. Then, marker peptides derived from the protein after enzymatic cleavage of the full wheat extracts were identified by LC-MS/MS. One of them was used as marker for quantitative determination on an UPLC/ESI-MS system by using its isotopically labelled analogue as internal standard, allowing to assess the protein content in the different samples. The CM3 allergenic proteins were found to greatly vary among different cultivation areas. PMID:23578625

  10. Pharmacological profile of the cyclic nociceptin/orphanin FQ analogues c[Cys10,14]N/OFQ(1-14)NH2 and c[Nphe1,Cys10,14]N/OFQ(1-14)NH2.

    PubMed

    Kitayama, M; Barnes, T A; Carra, G; McDonald, J; Calo, G; Guerrini, R; Rowbotham, D J; Smith, G; Lambert, D G

    2003-12-01

    In this study we describe the activity of two cyclic nociceptin/orphanin FQ (N/OFQ) peptides; c[Cys(10,14)]N/OFQ(1-14)NH(2) (c[Cys(10,14)]) and its [Nphe(1)] derivative c[Nphe(1),Cys(10,14)]N/OFQ(1-14)NH(2) (c[Nphe(1),Cys(10,14)]) in native rat and mouse and recombinant human N/OFQ receptors (NOP). Cyclisation may protect the peptide from metabolic degradation. In competition binding studies of rat, mouse and human NOP the following rank order pK(i) was obtained: N/OFQ(1-13)NH(2)(reference agonist)>N/OFQ=c[Cys(10,14)]>c[Nphe(1)Cys(10,14)]. In GTPgamma(35)S studies of Chinese hamster ovary cells expressing human NOP (CHO(hNOP)) c[Cys(10,14)] (pEC(50) 8.29) and N/OFQ(1-13)NH(2) (pEC(50) 8.57) were full agonists whilst c[Nphe(1)Cys(10,14)] alone was inactive. Following 30 min pre-incubation c[Nphe(1)Cys(10,14)] competitively antagonised the effects of N/OFQ(1-13)NH(2) with a pA(2) and slope factor of 6.92 and 1.01 respectively. In cAMP assays c[Cys(10,14)] (pEC(50) 9.29, E(max) 102% inhibition of the forskolin stimulated response), N/OFQ(1-13)NH(2) (pEC(50) 10.16, E(max) 103% inhibition) and c[Nphe(1)Cys(10,14)] (~80% inhibition at 10 microM) displayed agonist activity. In the mouse vas deferens c[Cys(10,14)] (pEC(50) 6.82, E(max) 89% inhibition of electrically evoked contractions) and N/OFQ(1-13)NH(2) (pEC(50) 7.47, E(max) 93% inhibition) were full agonists whilst c[Nphe(1)Cys(10,14)] alone was inactive. c[Nphe(1)Cys(10,14)] (10 microM) competitively antagonised the effects of N/OFQ(1-13)NH(2) with a pK(B) of 5.66. In a crude attempt to assess metabolic stability, c[Cys(10,14)] was incubated with rat brain membranes and then the supernatant assayed for remaining peptide. Following 60 min incubation 64% of the 1 nM added peptide was metabolised (compared with 54% for N/OFQ-NH(2)). In summary, we report that c[Cys(10,14)] is a full agonist with a small reduction in potency but no improvement in stability whilst c[Nphe(1)Cys(10,14)] displays tissue (antagonist in the

  11. Nonfatal and Fatal Self-Harm Injuries among Children Aged 10-14 Years--United States and Oregon, 2001-2003

    ERIC Educational Resources Information Center

    Vajani, Madhavi; Annest, Joseph L.; Crosby, Alex E.; Alexander, Janice D.; Millet, Lisa M.

    2007-01-01

    Fatal and nonfatal injuries due to suicidal behavior among younger adolescents are of growing concern for many communities. We examined the incidence and patterns of these injuries among persons aged 10-14 years using three databases, two national and a third from Oregon. Suffocation and firearm gunshot were the leading external causes of suicide;…

  12. Growth of rhodococcus S1 on anthracene.

    PubMed

    Tongpim, S; Pickard, M A

    1996-03-01

    Three slow-growing bacteria were isolated from a mixed culture enriched for growth on anthracene, using creosote-contaminated soil as the inoculum. Organisms were shown to use anthracene by the production of a clear zone around the colony after a mineral salts agar plate was sprayed with anthracene. All three bacteria were nonmotile, nonsporulating, gram-positive rods and stained acid-fast. Physiological and biochemical tests, GC content, and cell wall lipid patterns of whole cell methanolysates indicated that they belonged to the Nocardia-Mycobacterium-Rhodococcus group. On the basis of these characteristics and pyrolysis gas chromatography, they were assigned to the genus Rhodococcus. Growth of the isolates was slow on crystalline anthracene, giving a doubling time of 1.5-3 days, and they grew mainly on the crystal surface. When anthracene was supplied by precipitation from a solvent, doubling time was reduced to 1 day. All three isolates mineralized anthracene but not phenanthrene or naphthalene, nor could they grow on naphthalene, phenanthrene, fluorene, fluoranthene, acenaphthene, pyrene, chrysene, or naphthacene as sole carbon source. One isolate, Rhodococcus S1, was able to use 2-methylanthracene or 2-chloroanthracene as carbon source but not 1- or 9-substituted analogs. These results suggest that the initial enzyme attacking anthracene in these isolates has a narrow substrate specificity. PMID:8868237

  13. Studying the properties and response of a large volume (946 cm3) LaBr3:Ce detector with γ-rays up to 22.5 MeV

    NASA Astrophysics Data System (ADS)

    Mazumdar, I.; Gothe, D. A.; Anil Kumar, G.; Yadav, N.; Chavan, P. B.; Patel, S. M.

    2013-03-01

    This paper presents the results of our measurements and detailed simulations using GEANT4 to investigate the performance of a large volume (946 cm3) cylindrical (3.5 in.diameter×6 in.length) LaBr3:Ce detector. The properties of the detector have been studied using γ-rays from radioactive sources and in-beam reaction, from few hundred keV to 22.5 MeV. The salient features, which have been studied in-depth, are the uniformity and internal activity of the crystal, the energy and timing resolutions, linearity of the response up to 22.5 MeV, and efficiencies. A highly linear response has been observed by extracting the energy signal from a lower dynode and operating the PMT at a low voltage. The detector is to be primarily used for measuring high energy γ-rays spectra from Giant Dipole Resonance (GDR) decay studies.

  14. Exogenous S1P Exposure Potentiates Ischemic Stroke Damage That Is Reduced Possibly by Inhibiting S1P Receptor Signaling

    PubMed Central

    Moon, Eunjung; Han, Jeong Eun; Jeon, Sejin; Ryu, Jong Hoon; Choi, Ji Woong; Chun, Jerold

    2015-01-01

    Initial and recurrent stroke produces central nervous system (CNS) damage, involving neuroinflammation. Receptor-mediated S1P signaling can influence neuroinflammation and has been implicated in cerebral ischemia through effects on the immune system. However, S1P-mediated events also occur within the brain itself where its roles during stroke have been less well studied. Here we investigated the involvement of S1P signaling in initial and recurrent stroke by using a transient middle cerebral artery occlusion/reperfusion (M/R) model combined with analyses of S1P signaling. Gene expression for S1P receptors and involved enzymes was altered during M/R, supporting changes in S1P signaling. Direct S1P microinjection into the normal CNS induced neuroglial activation, implicating S1P-initiated neuroinflammatory responses that resembled CNS changes seen during initial M/R challenge. Moreover, S1P microinjection combined with M/R potentiated brain damage, approximating a model for recurrent stroke dependent on S1P and suggesting that reduction in S1P signaling could ameliorate stroke damage. Delivery of FTY720 that removes S1P signaling with chronic exposure reduced damage in both initial and S1P-potentiated M/R-challenged brain, while reducing stroke markers like TNF-α. These results implicate direct S1P CNS signaling in the etiology of initial and recurrent stroke that can be therapeutically accessed by S1P modulators acting within the brain. PMID:26576074

  15. Blocking S1P interaction with S1P{sub 1} receptor by a novel competitive S1P{sub 1}-selective antagonist inhibits angiogenesis

    SciTech Connect

    Fujii, Yasuyuki; Ueda, Yasuji; Ohtake, Hidenori; Ono, Naoya; Takayama, Tetsuo; Nakazawa, Kiyoshi; Igarashi, Yasuyuki; Goitsuka, Ryo

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer The effect of a newly developed S1P{sub 1}-selective antagonist on angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1} is a critical component of VEGF-related angiogenic responses. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vitro activity to inhibit angiogenesis. Black-Right-Pointing-Pointer S1P{sub 1}-selective antagonist showed in vivo activity to inhibit angiogenesis. Black-Right-Pointing-Pointer The efficacy of S1P{sub 1}-selective antagonist for anti-cancer therapies. -- Abstract: Sphingosine 1-phosphate receptor type 1 (S1P{sub 1}) was shown to be essential for vascular maturation during embryonic development and it has been demonstrated that substantial crosstalk exists between S1P{sub 1} and other pro-angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor. We developed a novel S1P{sub 1}-selective antagonist, TASP0277308, which is structurally unrelated to S1P as well as previously described S1P{sub 1} antagonists. TASP0277308 inhibited S1P- as well as VEGF-induced cellular responses, including migration and proliferation of human umbilical vein endothelial cells. Furthermore, TASP0277308 effectively blocked a VEGF-induced tube formation in vitro and significantly suppressed tumor cell-induced angiogenesis in vivo. These findings revealed that S1P{sub 1} is a critical component of VEGF-related angiogenic responses and also provide evidence for the efficacy of TASP0277308 for anti-cancer therapies.

  16. Conformationally Constrained, Stable, Triplet Ground State (S = 1) Nitroxide Diradicals. Antiferromagnetic Chains of S = 1 Diradicals

    SciTech Connect

    Rajca, Andrzej; Takahashi, Masahiro; Pink, Maren; Spagnol, Gaelle; Rajca, Suchada

    2008-06-30

    Nitroxide diradicals, in which nitroxides are annelated to m-phenylene forming tricyclic benzobisoxazine-like structures, have been synthesized and characterized by X-ray crystallography, magnetic resonance (EPR and {sup 1}H NMR) spectroscopy, as well as magnetic studies in solution and in solid state. For the octamethyl derivative of benzobisoxazine nitroxide diradical, the conformationally constrained nitroxide moieties are coplanar with the m-phenylene, leading to large values of 2J (2J/k > 200 K in solution and 2J/k >> 300 K in the solid state). For the diradical, in which all ortho and para positions of the m-phenylene are sterically shielded, distortion of the nitroxide moieties from coplanarity is moderate, such that the singlet-triplet gaps remain large in both solution (2J/k > 200 K) and the solid state (2J/k {approx} 400-800 K), though an onset of thermal depopulation of the triplet ground state is detectable near room temperature. These diradicals have robust triplet ground states with strong ferromagnetic coupling and good stability at ambient conditions. Magnetic behavior of the nitroxide diradicals at low temperature is best fit to the model of one-dimensional S = 1 Heisenberg chains with intrachain antiferromagnetic coupling. The antiferromagnetic coupling between the S = 1 diradicals may be associated with the methyl nitroxide C-H {hor_ellipsis} O contacts, including nonclassical hydrogen bonds. These unprecedented organic S = 1 antiferromagnetic chains are highly isotropic, compared to those of the extensively studied Ni(II)-based chains.

  17. Regulation of endothelial nitric oxide synthase activation in endothelial cells by S1P1 and S1P3.

    PubMed

    Tölle, M; Klöckl, L; Wiedon, A; Zidek, W; van der Giet, M; Schuchardt, M

    2016-08-01

    Endothelial nitric oxide synthase (eNOS) plays a crucial role in vascular homeostasis. Lysophospholipid interaction with sphingosine 1-phosphat (S1P) receptors results in eNOS activation in different cells. In endothelial cells, eNOS activation via S1P1 or S1P3 was shown controversially. The aim of this study is to investigate the meaning of both S1P receptors for eNOS activation in human endothelial cells. Therefore, several S1P1 and S1P3 agonists in combination with antagonists and specific RNAi approach were used. eNOS activation was measured in human umbilical vein endothelial cells (HUVEC) via DAF2-DA-based fluorescence microscopy. For investigation of the signaling pathway, agonists/antagonist studies, RNAi approach, Luminex™ multiplex, and Western Blot were used. In HUVEC, both the S1P1 agonist AUY954 as well as the S1P1,3 agonist FTY720P induced eNOS activation in a time- and dose-dependent manner. Other S1P1 agonists activated eNOS to a lesser extent. The AUY954-induced eNOS activation was blocked by the S1P1 antagonist W146, the combination of W146 and the S1P3 antagonist CAY10444 and the S1P1,3 antagonist VPC23019, but not by CAY10444 indicating the meaning of S1P1 for the AUY954-induced eNOS activation. The FTY720P-induced eNOS activation was blocked only by the combination of W146 and CAY10444 and the combined S1P1,3 antagonist VPC23019, but not by W146 or CAY10444 indicating the importance of both S1P1 and S1P3 for FTY720-induced eNOS activation. These results were confirmed using specific siRNA against S1P1 and S1P3. The S1P1,3 activation results in Akt phosphorylation and subsequent activation of eNOS via phosphorylation at serine(1177) and dephosphorylation at threonine(495). Beside former investigations with rather unspecific S1P receptor activation these data show potent selective S1P1 activation by using AUY954 and with selective S1P receptor inhibition evidence was provided that both S1P1 and S1P3 lead to downstream activation of eNOS in

  18. Roles for lysophospholipid S1P receptors in multiple sclerosis.

    PubMed

    Noguchi, Kyoko; Chun, Jerold

    2011-02-01

    Sphingosine 1-phosphate (S1P) signaling in the treatment of multiple sclerosis (MS) has been highlighted by the efficacy of FTY720 (fingolimod), which upon phosphorylation can modulate S1P receptor activities. FTY720 has become the first oral treatment for relapsing MS that was approved by the FDA in September 2010. Phosphorylated FTY720 modulates four of the five known S1P receptors (S1P(1), S1P(3), S1P(4), and S1P(5)) at high affinity. Studies in human MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have revealed that FTY720 exposure alters lymphocyte trafficking via sequestration of auto-aggressive lymphocytes within lymphoid organs, representing the current understanding of its mechanism of action. These effects primarily involve S1P(1), which is thought to attenuate inflammatory insults in the central nervous system (CNS). In addition, FTY720's actions may involve direct effects on S1P receptor-mediated signaling in CNS cells, based upon the known expression of S1P receptors in CNS cell types relevant to MS, access to the CNS through the blood-brain barrier (BBB), and in vitro studies. These data implicate lysophospholipid signaling--via S1P(1) and perhaps other lysophospholipid receptors--in therapeutic approaches to MS and potentially other diseases with immunological and/or neurological components. PMID:20979571

  19. An AFM-based surface oxidation process for heavily carbon-doped p-type GaAs with a hole concentration of 1.5×1021 cm-3

    NASA Astrophysics Data System (ADS)

    Shirakashi, J.-I.; Matsumoto, K.; Konagai, M.

    Under appropriate bias conditions in ambient humidity, AFM can be used to selectively oxidize the surface of electronic materials such as metals and semiconductors. Therefore, an AFM-based surface modification technique would be a powerful tool for fabricating nanometer-sized metal (M)/insulator (I) or semiconductor (S)/insulator (I) junction structures. Heavily carbon-doped p-type GaAs with a hole concentration of 1.5×1021 cm-3 is also of great interest for application to novel device structures, because the carrier concentration is comparable to that of normal metals. Selective surface oxidation of carbon-doped p-type GaAs was achieved using a negatively biased conductive tip. The oxidation shown here was carried out under 20-25% ambient humidity. By changing the applied bias voltage and the scanning speed of the cantilever, the size of the modified structure wires was precisely controlled, with a feature size of 10 nm. These results suggest that GaAs-based devices with ultra-small SIS junction systems could be realized using the AFM-based surface oxidation process.

  20. Resonating Valence Bond states for low dimensional S=1 antiferromagnets

    NASA Astrophysics Data System (ADS)

    Liu, Zheng-Xin; Zhou, Yi; Ng, Tai-Kai

    2014-03-01

    We study S = 1 spin liquid states in low dimensions. We show that the resonating-valence-bond (RVB) picture of S = 1 / 2 spin liquid state can be generalized to S = 1 case. For S = 1 system, a many-body singlet (with even site number) can be decomposed into superposition of products of two-body singlets. In other words, the product states of two-body singlets, called the singlet pair states (SPSs), are over complete to span the Hilbert space of many-body singlets. Furthermore, we generalized fermionic representation and the corresponding mean field theory and Gutzwiller projected stats to S = 1 models. We applied our theory to study 1D anti-ferromagnetic bilinear-biquadratic model and show that both the ground states (including the phase transition point) and the excited states can be understood excellently well within the framework. Our method can be applied to 2D S = 1 antiferromagnets.

  1. 26 CFR 1.414(s)-1 - Definition of compensation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... prior regulation provisions of § 1.414(s)-1T. (See § 1.414(s)-1T as contained in the CFR edition revised... to the extent necessary to satisfy the requirements of 29 CFR 2530.204-2(d) (regarding double... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Definition of compensation. 1.414(s)-1 Section...

  2. Precision polarizability measurements of atomic cesium's 8 s 2S1 / 2 and 9 s 2S1 / 2 states

    NASA Astrophysics Data System (ADS)

    Weaver, Hannah; Kortyna, Andrew

    2013-05-01

    We report hyperfine-resolved scalar polarizabilities for cesium's 8 s 2S1 / 2 and 9 s 2S1 / 2 states using resonant two-photon spectroscopy. Two single-mode, external-cavity diode lasers drive the 6 s 2S1 / 2 --> 6 p 2P1 / 2 --> ns 2S1 / 2 transition (n = 8 or 9). Both laser beams are split and counter-propagate through an effusive beam and a vapor cell. An electric field applied across two parallel plates imposes Stark shifts on the ns 2S1 / 2 levels in the effusive beam. Electric-field strengths are measured in situ. The laser frequency is calibrated in the vapor cell using a phase modulation technique, with the modulation frequency referenced to the ground-state hyperfine splitting of atomic rubidium. Our measured 8 s 2S1 / 2 polarizability, 38370 +/- 380 a03, agrees with previous theory and experiments. Our measured 9 s 2S1 / 2 polarizability, 150700 +/- 1100 a03, agrees within two sigma of theory, but we are unaware of previous measurements. We also verify that these polarizabilities are independent of the hyperfine levels, placing upper limits on the differential polarizabilities of 200 +/- 260 a03 for the 8 s 2S1 / 2 state and 490 +/- 450 a03 for the 9 s 2S1 / 2 state. Supported by the National Science Foundation under Grant PHY-0653107.

  3. Determination of inorganic ionic mercury down to 5x10(-14) mol l(-1) by differential-pulse anodic stripping voltammetry.

    PubMed

    Meyer, S; Scholz, F; Trittler, R

    1996-09-01

    A new method is described for the reliable and ultrasensitive determination of inorganic ionic mercury, using differential-pulse anodic stripping voltammetry on a glassy carbon electrode. It has been possible to determine mercury down to a concentration of 5x10(-14) mol l(-1) (the lowest detection limit ever reported for a voltammetric method). This success was achieved by using a thiocyanate electrolyte and relatively long deposition times. The mercury ions are stabilized in the solution by the formation of strong thiocyanate complexes. This leads to a highly reproducible cathodic plating and anodic dissolution of mercury. A speciation analysis allowing to distinguish between dissolved atomic and ionic mercury in water is possible. PMID:15048362

  4. Development of regional future climate change scenarios in South America using the Eta CPTEC/HadCM3 climate change projections: climatology and regional analyses for the Amazon, São Francisco and the Paraná River basins

    NASA Astrophysics Data System (ADS)

    Marengo, Jose A.; Chou, Sin Chan; Kay, Gillian; Alves, Lincoln M.; Pesquero, José F.; Soares, Wagner R.; Santos, Daniel C.; Lyra, André A.; Sueiro, Gustavo; Betts, Richard; Chagas, Diego J.; Gomes, Jorge L.; Bustamante, Josiane F.; Tavares, Priscila

    2012-05-01

    The objective of this study is to assess the climate projections over South America using the Eta-CPTEC regional model driven by four members of an ensemble of the Met Office Hadley Centre Global Coupled climate model HadCM3. The global model ensemble was run over the twenty-first century according to the SRES A1B emissions scenario, but with each member having a different climate sensitivity. The four members selected to drive the Eta-CPTEC model span the sensitivity range in the global model ensemble. The Eta-CPTEC model nested in these lateral boundary conditions was configured with a 40-km grid size and was run over 1961-1990 to represent baseline climate, and 2011-2100 to simulate possible future changes. Results presented here focus on austral summer and winter climate of 2011-2040, 2041-2070 and 2071-2100 periods, for South America and for three major river basins in Brazil. Projections of changes in upper and low-level circulation and the mean sea level pressure (SLP) fields simulate a pattern of weakening of the tropical circulation and strengthening of the subtropical circulation, marked by intensification at the surface of the Chaco Low and the subtropical highs. Strong warming (4-6°C) of continental South America increases the temperature gradient between continental South America and the South Atlantic. This leads to stronger SLP gradients between continent and oceans, and to changes in moisture transport and rainfall. Large rainfall reductions are simulated in Amazonia and Northeast Brazil (reaching up to 40%), and rainfall increases around the northern coast of Peru and Ecuador and in southeastern South America, reaching up to 30% in northern Argentina. All changes are more intense after 2040. The Precipitation-Evaporation (P-E) difference in the A1B downscaled scenario suggest water deficits and river runoff reductions in the eastern Amazon and São Francisco Basin, making these regions susceptible to drier conditions and droughts in the future.

  5. Degenerative Sacrolisthesis of S1-S2: A Case Report

    PubMed Central

    Rajendra, Thakre Kunwar; Issac, Thomas; Swamy, B Mallikarjuna

    2015-01-01

    Introduction: Degenerative spondylolisthesis (DS) is usually seen at L4-L5 level and less frequently at L5-S1 level. This is a rare case report of spondylolisthesis of S1 over S2 with lumbarization of S1. Lumbarization of S1 is seen in just 1-2% of the population and to have spondylolisthesis in this segment is even rarer. The purpose is to report a rare case of DS at S1-S2 level. Case Report: This is a single case report of a 66-year-old gentleman who presented with complains of lower backache for 2 years and acute retention of urine to the emergency department. Detailed clinical and radiological evaluation of the spine was done which revealed lumbarization of S1 with spondylolisthesis at S1-S2 and facetal hypertrophy at L5, S1, and S2. He underwent decompression and stabilization at L5, S1, and S2 along with placement of autologous bone graft. The bladder symptoms disappeared after 3 weeks. At 1-year follow-up, patient’s clinical symptoms were relieved, and he improved clinically. Conclusion: To the best of our knowledge, this is probably the first case of DS of sacral vertebrae to be reported in English literature. The prevalence of complete lumbarization is around 1.8% and to get spondylolisthesis in this segment is even rarer, hence the lack of literature in this regard. Since this is the first of its kind of case, further case series or longitudinal studies of such cases may help understand better the pathomechanics related to spondylolisthesis at this level. PMID:27299082

  6. 7S(1/2) ? 9S(1/2) two-photon spectroscopy of trapped francium.

    PubMed

    Simsarian, J E; Shi, W; Orozco, L A; Sprouse, G D; Zhao, W Z

    1996-12-01

    We report on the spectroscopic measurement of the (210)Fr 9S(1/2) energy obtained by two-photon excitation of atoms confined and cooled in a magneto-optic trap. The resonant intermediate level 7P(3/2) is the upper state of the trapping transition. We have measured the energy difference between the 9S(1/2) state and the 7S(1/2) ground state to be 25 671.021 +/- 0.006 cm(-1). PMID:19881852

  7. The reaction of pristane (2,6,10,14-tetramethylpentadecane) with radiolytically generated reactive oxygen intermediates results in a stable genotoxic compound as assessed by the SOS chromotest.

    PubMed

    Janz, S; Brede, O; Müller, J

    1991-07-01

    The most widely studied model of plasmacytomagenesis is the induction of plasmacytomas in BALB/c mice by i.p. injections of the isoalkane pristane (2,6,10,14-tetramethylpentadecane). Employing a simple quantitative and well-established short-term bacterial genotoxicity assay, the SOS chromotest, as a model system, we have investigated whether pristane may potentially be involved in causing or modulating the genotoxic events thought to induce plasma cell tumorigenesis. We found that incorporation of pristane into the cell membranes enhance the SOS response in Escherichia coli PQ37 and PQ300 induced by gamma-radiation under hyperoxic conditions. Moreover, the oxidation of pristane by radiolytically generated reactive oxygen intermediates yielded a stable, genotoxic product active on E. coli PQ300, a SOS tester strain designed to detect oxidative genotoxins. We discuss these findings in relation to the tumor-promoting role of the chronic i.p. inflammation that accompanies plasmacytomagenesis and conclude that, under these specific conditions, pristane may possess a previously unrecognized genotoxic activity in its tumorigenic potential. PMID:2070489

  8. The first results of series of Plasma - Progress active experiments carried out on September 19-24, 2007 and February 10-14, 2008.

    NASA Astrophysics Data System (ADS)

    Medvedev, Andrey; Khakhinov, Vitaliy; Kushnarev, Dmitriy; Lebedev, Valentin; Potekhin, Alexander; Shpynev, Boris; Ratovsky, Konstantin

    A sequence of active space experiments was carried out in collaboration with the Korolev's Rocket Space Corporation "Energy", the Central Research Institute for Machine-Building and the Institute of Solar-Terrestrial Physics Russian Academy of Sciences, Siberian Branch (ISTP SB RAS) on September 19-24, 2007 and February 10-14, 2008. Orbital maneuvering subsystem (OMS) engines of transport spacecraft (TSC) Progress were used as a source of disturbances for ionospheric and radar signature characteristics. The altitude of the TSC orbit was about 340 km. In order to perform this experiment the ground-base Radio-Optic Complex of ISTP SB RAS including Irkutsk Incoherent Scatter Radar has been involved. Each burn started once in day exactly over the radar. The exhaust directions as well as amount of injected products were changed from fly to fly. During "PLASMA-PROGRESS" experiments high precision measurements of TCV coordinate and reflecting characteristics and space-time disturbances of plasma parameters have been executed. Multiple radar beams allowed us to simultaneously observe both the modified and unmodified ionosphere. The analysis of the data has shown that burn of the TSC even relatively weak engines causes the considerable changes both in the electron concentration profile and in the value of the TSC radar cross-section.

  9. Direct measurements of the non-DD cross section {sigma}{sub {psi}}{sub (3770){yields}}{sub non-DD} at E{sub cm}=3.773 GeV and the branching fraction for {psi}(3770){yields}non-DD

    SciTech Connect

    Ablikim, M.; Bai, J. Z.; Cai, X.; Chen, H. S.; Chen, H. X.; Chen, J. C.; Chen, Jin; Chen, Y. B.; Chu, Y. P.; Deng, Z. Y.; Du, S. X.; Fang, J.; Fang, S. S.; Gao, C. S.; Gu, S. D.; Guo, Y. N.; He, K. L.; Heng, Y. K.; Hu, H. M.; Hu, T.

    2007-12-15

    By analyzing the data collected at the center-of-mass energy E{sub cm}=3.773 GeV and below the DD meson pair production threshold with the BES-II detector at the BEPC Collider, we directly measured the observed non-DD cross section of {psi}(3770) decay to be {sigma}{sub {psi}}{sub (3770){yields}}{sub non-DD}{sup obs}=(0.95{+-}0.35{+-}0.29) nb at E{sub cm}=3.773 GeV, and the branching fraction BF[{psi}(3770){yields}non-DD]=(13.4{+-}5.0{+-}3.6)% for inclusive non-DD decay of {psi}(3770). We also determined the cross section for DD meson pair production to be {sigma}{sub DD}{sup obs}=(6.12{+-}0.37{+-}0.23) nb at E{sub cm}=3.773 GeV.

  10. Structural biology of the S1P1 receptor.

    PubMed

    Hanson, Michael A; Peach, Robert

    2014-01-01

    The sphingosine 1 phosphate receptor family has been studied widely since the initial discovery of its first member, endothelium differentiation gene 1. Since this initial discovery, the family has been renamed and the primary member of the family, the S1P1 receptor, has been targeted for a variety of disease indications and successfully drugged for the treatment of patients with relapsing multiple sclerosis. Recently, the three-dimensional structure of the S1P1 receptor has been determined by X-ray crystallography and the specifics of the sphingosine 1 phosphate ligand binding pocket mapped. Key structural features for the S1P1 receptor will be reviewed and the potential binding modes of additional pharmacologically active agents against the receptor will be analyzed in an effort to better understand the structural basis of important receptor-ligand interactions. PMID:24728592

  11. S1-hypersensitive sites in eukaryotic promoter regions.

    PubMed Central

    Evans, T; Schon, E; Gora-Maslak, G; Patterson, J; Efstratiadis, A

    1984-01-01

    We have examined by fine mapping the S1 nuclease-hypersensitivity of the 5' flanking regions of the human beta-globin and rat preproinsulin II genes and of the SV40 origin/enhancer region. In all cases S1-hypersensitive sites are located in known or presumed promoter/regulatory regions. Though a consensus DNA sequence is not evident, all of these sites reside in predominantly homopurine-homopyrimidine stretches. The alternate (non-B) DNA structure which is revealed by the enzymatic probe is a sequence-dependent feature of a short stretch of DNA, which is retained upon transplantation into a foreign environment. The alternate structure exhibits S1-nicking patterns uniquely different from those associated with the presence of Z-DNA. Images PMID:6095186

  12. S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer: A meta-analysis

    PubMed Central

    Yang, Jian; Zhou, Yan; Min, Ke; Yao, Qiang; Xu, Chun-Ni

    2014-01-01

    AIM: To assess the efficacy and tolerability of S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer (AGC). METHODS: We extracted reported endpoints, including overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), objective response rate (ORR) and adverse effects, from randomized controlled trials identified in PubMed, the Cochrane library, Science Direct, EMBASE and American Society of Clinical Oncology meetings. Stata software was used to calculate the pooled values. RESULTS: Seven randomized controlled trials involving 2176 patients were included in this meta-analysis. Compared to non-S-1-based regimens, the use of S-1-based regimens were associated with an increase in ORR (RR = 1.300; 95%CI: 1.028-1.645); OS (HR = 0.89; 95%CI: 0.81-0.99; P = 0.025), TTF (HR = 0.83; 95%CI: 0.75-0.92; P = 0.000), and a lower risk of febrile neutropenia (RR = 0.225; P = 0.000) and stomatitis (RR = 0.230; P = 0.032). OS, PFS and TTF were prolonged, especially in the Asian population. In subgroup analysis, statistically significant increases in ORR (RR = 1.454; P = 0.029), OS (HR = 0.895; P = 0.041) and TTF (HR = 0.832; P = 0.000) were found when S-1-based chemotherapy was compared to 5-fluorouracil (5-FU)-based chemotherapy. The incidence of leukopenia (RR = 0.584; P = 0.002) and stomatitis (RR = 0.230; P = 0.032) was higher in the 5-FU-based arm. S-1-based regimens had no advantage in ORR, OS, PFS, TTF and grade 3 or 4 adverse events over capecitabine-based regimens. CONCLUSION: S-1-based chemotherapy may be a good choice for AGC because of longer survival times, better tolerance and more convenient use. PMID:25206296

  13. The S=1 Underscreened Anderson Lattice model for Uranium compounds

    NASA Astrophysics Data System (ADS)

    Thomas, C.; Simões, A. S. R.; Iglesias, J. R.; Lacroix, C.; Perkins, N. B.; Coqblin, B.

    2011-01-01

    Magnetic properties of uranium and neptunium compounds showing coexistence of the Kondo effect and ferromagnetic order are investigated within the degenerate Anderson Lattice Hamiltonian, describing a 5f2 electronic configuration with S = 1 spins. Through the Schrieffer-Wolff transformation, both an exchange Kondo interaction for the S = 1 f-spins and an effective f-band term are obtained, allowing to describe the coexistence of Kondo effect and ferromagnetic ordering and a weak delocalization of the 5f-electrons. We calculate the Kondo and Curie temperatures and we can account for the pressure dependence of the Curie temperature of UTe.

  14. Winding Hopfions on R2×S1

    NASA Astrophysics Data System (ADS)

    Kobayashi, Michikazu; Nitta, Muneto

    2013-11-01

    We study Hopfions in the Faddeev-Skyrme model with potential terms on R2×S1. Apart from the conventional Hopfions, there exist winding Hopfions, that is, the lump (baby Skyrmion) strings with the lump charge Q with the U(1) modulus twisted P times along S1, having the Hopf charge PQ. We consider two kinds of potential terms, that is, the potential linear in the field and the ferromagnetic potential with two easy axes, and present stable solutions numerically. We also point out that a Q-lump carries the unit Hopf charge per the period in d=2+1.

  15. Bacterial versus human sphingosine-1-phosphate lyase (S1PL) in the design of potential S1PL inhibitors.

    PubMed

    Sanllehí, Pol; Abad, José-Luis; Casas, Josefina; Bujons, Jordi; Delgado, Antonio

    2016-09-15

    A series of potential active-site sphingosine-1-phosphate lyase (S1PL) inhibitors have been designed from scaffolds 1 and 2, arising from virtual screening using the X-ray structures of the bacterial (StS1PL) and the human (hS1PL) enzymes. Both enzymes are very similar at the active site, as confirmed by the similar experimental kinetic constants shown by the fluorogenic substrate RBM13 in both cases. However, the docking scoring functions used probably overestimated the weight of electrostatic interactions between the ligands and key active-site residues in the protein environment, which may account for the modest activity found for the designed inhibitors. In addition, the possibility that the inhibitors do not reach the enzyme active site should not be overlooked. Finally, since both enzymes show remarkable structural differences at the access channel and in the proximity to the active site cavity, caution should be taken when designing inhibitors acting around that area, as evidenced by the much lower activity found in StS1PL for the potent hS1PL inhibitor D. PMID:27475537

  16. Human alpha s1-casein: purification and characterization.

    PubMed

    Rasmussen, L K; Due, H A; Petersen, T E

    1995-05-01

    The human counterpart of alpha s1-casein has been purified by a combination of gel-filtration and ion-exchange chromatography under denaturing conditions. SDS-PAGE analysis revealed the presence of a diffuse ladder with a high molecular mass which upon reduction was replaced by several closely spaced bands of lower molecular masses and a broad diffuse band corresponding to kappa-casein. Amino acid sequence analysis of the closely spaced bands all resulted in the same N-terminal sequence which was found to be homologous with alpha s1-casein from other species. Sequence analysis of a major radiolabelled tryptic peptide from purified 14C-carboxymethylated alpha s1-casein demonstrated that the protein contains at least two cysteine residues. As judged by SDS-PAGE in the presence or absence of a reducing agent, the molecular structure of the polymers constituting the ladder is composed of heteropolymers of alpha s1- and kappa-casein cross-linked by disulfide bonds. PMID:7749638

  17. Late-stage optimization of a tercyclic class of S1P3-sparing, S1P1 receptor agonists.

    PubMed

    Horan, Joshua C; Kuzmich, Daniel; Liu, Pingrong; DiSalvo, Darren; Lord, John; Mao, Can; Hopkins, Tamara D; Yu, Hui; Harcken, Christian; Betageri, Raj; Hill-Drzewi, Melissa; Patenaude, Lori; Patel, Monica; Fletcher, Kimberly; Terenzzio, Donna; Linehan, Brian; Xia, Heather; Patel, Mita; Studwell, Debbie; Miller, Craig; Hickey, Eugene; Levin, Jeremy I; Smith, Dustin; Kemper, Raymond A; Modis, Louise K; Bannen, Lynne C; Chan, Diva S; Mac, Morrison B; Ng, Stephanie; Wang, Yong; Xu, Wei; Lemieux, René M

    2016-01-15

    Poor solubility and cationic amphiphilic drug-likeness were liabilities identified for a lead series of S1P3-sparing, S1P1 agonists originally developed from a high-throughput screening campaign. This work describes the subsequent optimization of these leads by balancing potency, selectivity, solubility and overall molecular charge. Focused SAR studies revealed favorable structural modifications that, when combined, produced compounds with overall balanced profiles. The low brain exposure observed in rat suggests that these compounds would be best suited for the potential treatment of peripheral autoimmune disorders. PMID:26687487

  18. Is the addition of cisplatin to S-1 better than S-1 alone for patients with advanced gastroesophageal cancer?

    PubMed

    Ajani, Jaffer A

    2008-09-01

    The investigators of the recent phase III SPIRITS trial found that the addition of cisplatin to S-1 (a fourth generation oral fluoropyrimidine) provided a significant overall survival advantage (P = 0.04) over treatment with S-1 alone among previously untreated patients with advanced gastric cancer. In addition, the combination had an acceptable safety profile. This trial establishes a new first-line standard treatment for patients with advanced gastric cancer in Japan. Level 1 evidence for prolonged survival of patients with advanced gastroesophageal cancer has been established for docetaxel (V-325 trial) and cisplatin (SPIRITS trial) but not for S-1. Fluoropyrimidines (S-1 included) have been considered part of standard front-line therapy without the establishment of level 1 evidence for prolonging survival. The future lies in the rapid incorporation of biologic agents in combination with cytotoxics, with a continued focus on safety and convenience, and efforts to individualize therapy for each patient. Individualized therapy may be defined as the selection of optimum treatment for a specific patient on the basis of knowledge of the cancer's genetic and epigenetic alterations and the patient's genotype. PMID:18628737

  19. Molecular structure of Si_xS_(1-x) glasses

    NASA Astrophysics Data System (ADS)

    Wang, Y.; Boolchand, P.

    2000-03-01

    Bulk Si_xS_1-x glasses in the 0.15S_1/2)4 tetrahedra, S_8-ring and Sn chains. The observed lineshapes change systematically with x, in a manner qualitatively similar to the case of corresponding Selenide glasses( D. Selvanathan, W. J. Bresser, P. Boolchand, B. Goodman Solid State Comm. 111, 619(1999)). Glass transition temperatures established by T-modulated DSC show an increase with x. Results of Raman and MDSC will be correlated, and discussed in relation to the nature of stiffness transitions anticipated in this binary glass system near x ~0.20.

  20. The Global S_1 Tide in Earth's Nutation

    NASA Astrophysics Data System (ADS)

    Schindelegger, Michael; Einšpigel, David; Salstein, David; Böhm, Johannes

    2016-05-01

    Diurnal S_1 tidal oscillations in the coupled atmosphere-ocean system induce small perturbations of Earth's prograde annual nutation, but matching geophysical model estimates of this Sun-synchronous rotation signal with the observed effect in geodetic Very Long Baseline Interferometry (VLBI) data has thus far been elusive. The present study assesses the problem from a geophysical model perspective, using four modern-day atmospheric assimilation systems and a consistently forced barotropic ocean model that dissipates its energy excess in the global abyssal ocean through a parameterized tidal conversion scheme. The use of contemporary meteorological data does, however, not guarantee accurate nutation estimates per se; two of the probed datasets produce atmosphere-ocean-driven S_1 terms that deviate by more than 30 μ as (microarcseconds) from the VLBI-observed harmonic of -16.2+i113.4 μ as. Partial deficiencies of these models in the diurnal band are also borne out by a validation of the air pressure tide against barometric in situ estimates as well as comparisons of simulated sea surface elevations with a global network of S_1 tide gauge determinations. Credence is lent to the global S_1 tide derived from the Modern-Era Retrospective Analysis for Research and Applications (MERRA) and the operational model of the European Centre for Medium-Range Weather Forecasts (ECMWF). When averaged over a temporal range of 2004 to 2013, their nutation contributions are estimated to be -8.0+i106.0 μ as (MERRA) and -9.4+i121.8 μ as (ECMWF operational), thus being virtually equivalent with the VLBI estimate. This remarkably close agreement will likely aid forthcoming nutation theories in their unambiguous a priori account of Earth's prograde annual celestial motion.

  1. Angular momentum budget of the radiational S1 ocean tide

    NASA Astrophysics Data System (ADS)

    Schindelegger, Michael; Dobslaw, Henryk; Poropat, Lea; Salstein, David; Böhm, Johannes

    2016-04-01

    The balance of diurnal S1 oceanic angular momentum (OAM) variations through torques at the sea surface and the bottom topography is validated using both a barotropic and a baroclinic numerical tide model. This analysis discloses the extent to which atmosphere-driven S1 forward simulations are reliable for use in studies of high-frequency polar motion and changes in length-of-day. Viscous and dissipative torques associated with wind stress, bottom friction, as well as internal tidal energy conversion are shown to be small, and they are overshadowed by gravitational and pressure-related interaction forces. In particular, the zonal OAM variability of S1 is almost completely balanced by the water pressure torque on the local bathymetry, whereas in the prograde equatorial case also the air pressure torque on the seafloor as well as ellipsoidal contributions from the non-spherical atmosphere and solid Earth must be taken into account. Overall, the OAM budget is well closed in both the axial and the equatorial directions, thus allowing for an identification of the main diurnal angular momentum sinks in the ocean. The physical interaction forces are found to be largest at shelf breaks and continental slopes in low latitudes, with the most dominant contribution coming from the Indonesian archipelago.

  2. S1P metabolism in cancer and other pathological conditions

    PubMed Central

    Leong, Weng In

    2010-01-01

    Nearly two decades ago, the sphingolipid metabolite sphingosine 1-phosphate was discovered to function as a lipid mediator and regulator of cell proliferation. Since that time, sphingosine 1-phosphate has been shown to mediate a diverse array of fundamental biological processes including cell proliferation, migration, invasion, angiogenesis, vascular maturation and lymphocyte trafficking. Sphingosine 1-phosphate acts primarily via signaling through five ubiquitously expressed G protein-coupled receptors. Intracellular sphingosine 1-phosphate molecules are transported extracellularly and gain access to its cognate receptors for autocrine and paracrine fashion and for signaling at distant sites reached through blood and lymphatic circulation systems. Intracellular pools of sphingosine 1-phosphate available for signaling are tightly regulated by three enzymes that include sphinosine kinase, S1P lyase and S1P phosphatase. Alterations in S1P levels as well as the enzymes involved in its synthesis and catabolism have been observed in many types of malignancy. These enzymes are being evaluated for their role in mediating cancer formation and progression, as well as their potential to serve as targets of anti-cancer therapeutics. In this review, the impact of sphingosine 1-phosphate, its cognate receptors, and the enzymes of sphingosine 1-phosphate metabolism on cell survival, apoptosis, autophagy, cellular transformation, invasion, angiogenesis and hypoxia in relation to cancer biology and treatment are discussed. PMID:20167244

  3. Search for ammonia in comet C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Faggi, S.; Codella, C.; Tozzi, G. P.; Comoretto, G.; Crovisier, J.; Nesti, R.; Panella, D.; Boissier, J.; Brucato, J. R.; Bolli, P.; Massi, F.; Tofani, G.

    2015-12-01

    Comets are uniquely pristine bodies providing unique insights about the formation of our Solar System. In this work, we focus on a dynamically new comet as it enters the inner Solar System for the first time after residing for billion of years in the Oort Cloud. Such comets are particularly important because they are thought to be not differentiated by solar radiation and they are supposed to have a large quantity of organic matter close to the surface. Here we report the results of a search for NH3(1,1) emission at 23.7 GHz towards comet C/2012 S1 (ISON) using a new dual-feed K band receiver mounted on the Medicina 32-m antenna. We observed the comet close to its perihelion, from 25 to 29 November 2013, when its heliocentric distance changed from 0.25 AU to 0.03 AU. We derive an upper limit of Q(NH3) of about 2.5×1029 mol s-1 on 26 November, that is consistent with the last peak of water production rate of ∼2×1030 mol s-1 within the last few days before the perihelion.

  4. Argyres-Douglas theories, S 1 reductions, and topological symmetries

    NASA Astrophysics Data System (ADS)

    Buican, Matthew; Nishinaka, Takahiro

    2016-01-01

    In a recent paper, we proposed closed-form expressions for the superconformal indices of the ({A}1,{A}2n-3) and ({A}1,{D}2n) Argyres-Douglas (AD) superconformal field theories (SCFTs) in the Schur limit. Following up on our results, we turn our attention to the small S 1 regime of these indices. As expected on general grounds, our study reproduces the S 3 partition functions of the resulting dimensionally reduced theories. However, we show that in all cases—with the exception of the reduction of the ({A}1,{D}4) SCFT—certain imaginary partners of real mass terms are turned on in the corresponding mirror theories. We interpret these deformations as R symmetry mixing with the topological symmetries of the direct S 1 reductions. Moreover, we argue that these shifts occur in any of our theories whose four-dimensional { N }=2 superconformal U{(1)}R symmetry does not obey an SU(2) quantization condition. We then use our R symmetry map to find the four-dimensional ancestors of certain three-dimensional operators. Somewhat surprisingly, this picture turns out to imply that the scaling dimensions of many of the chiral operators of the four-dimensional theory are encoded in accidental symmetries of the three-dimensional theory. We also comment on the implications of our work on the space of general { N }=2 SCFTs.

  5. Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-{kappa}B ligand (RANKL) expression in rheumatoid arthritis

    SciTech Connect

    Takeshita, Harunori; Kitano, Masayasu; Iwasaki, Tsuyoshi; Kitano, Sachie; Tsunemi, Sachi; Sato, Chieri; Sekiguchi, Masahiro; Azuma, Naoto; Miyazawa, Keiji; Hla, Timothy; Sano, Hajime

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer MH7A cells and CD4{sup +} T cells expressed S1P1 and RANKL. Black-Right-Pointing-Pointer S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells. Black-Right-Pointing-Pointer The effect of S1P in MH7A cells was inhibited by specific Gi/Go inhibitors. -- Abstract: Sphingosine 1-phosphate (S1P)/S1P receptor 1 (S1P1) signaling plays an important role in synovial cell proliferation and inflammatory gene expression by rheumatoid arthritis (RA) synoviocytes. The purpose of this study is to clarify the role of S1P/S1P1 signaling in the expression of receptor activator of NF-{kappa}B ligand (RANKL) in RA synoviocytes and CD4{sup +} T cells. We demonstrated MH7A cells, a human RA synovial cell line, and CD4{sup +} T cells expressed S1P1 and RANKL. Surprisingly, S1P increased RANKL expression in MH7A cells and CD4{sup +} T cells in a dose-dependent manner. Moreover, S1P enhanced RANKL expression induced by stimulation with TNF-{alpha} in MH7A cells and CD4{sup +} T cells. These effects of S1P in MH7A cells were inhibited by pretreatment with PTX, a specific Gi/Go inhibitor. These findings suggest that S1P/S1P1 signaling may play an important role in RANKL expression by MH7A cells and CD4{sup +} T cells. S1P/S1P1 signaling of RA synoviocytes is closely connected with synovial hyperplasia, inflammation, and RANKL-induced osteoclastogenesis in RA. Thus, regulation of S1P/S1P1 signaling may become a novel therapeutic target for RA.

  6. Dynamical instability in the S =1 Bose-Hubbard model

    NASA Astrophysics Data System (ADS)

    Asaoka, Rui; Tsuchiura, Hiroki; Yamashita, Makoto; Toga, Yuta

    2016-01-01

    We study the dynamical instabilities of superfluid flows in the S =1 Bose-Hubbard model. The time evolution of each spin component in a condensate is calculated based on the dynamical Gutzwiller approximation for a wide range of interactions, from a weakly correlated regime to a strongly correlated regime near the Mott-insulator transition. Owing to the spin-dependent interactions, the superfluid flow of the spin-1 condensate decays at a different critical momentum from a spinless case when the interaction strength is the same. We furthermore calculate the dynamical phase diagram of this model and clarify that the obtained phase boundary has very different features depending on whether the average number of particles per site is even or odd. Finally, we analyze the density and spin modulations that appear in association with the dynamical instability. We find that spin modulations are highly sensitive to the presence of a uniform magnetic field.

  7. Effect of anisotropy in the S=1 underscreened Kondo lattice

    NASA Astrophysics Data System (ADS)

    Thomas, Christopher; da Rosa Simões, Acirete S.; Lacroix, Claudine; Iglesias, José Roberto; Coqblin, Bernard

    2014-12-01

    We study the effect of crystal field anisotropy in the underscreened S=1 Kondo lattice model. Starting from the two orbital Anderson lattice model and including a local anisotropy term, we show, through Schrieffer-Wolff transformation, that local anisotropy is equivalent to an anisotropic Kondo interaction (J∥≠J⊥). The competition and coexistence between ferromagnetism and Kondo effect in this effective model is studied within a generalized mean-field approximation. Several regimes are obtained, depending on the parameters, exhibiting or not coexistence of magnetic order and Kondo effect. Particularly, we show that a re-entrant Kondo phase at low temperature can be obtained. We are also able to describe phases where the Kondo temperature is smaller than the Curie temperature (TK

  8. Confinement and power balance in the S-1 spheromak

    SciTech Connect

    Levinton, F.M.; Meyerhofer, D.D.; Mayo, R.M.; Janos, A.C.; Ono, Y.; Ueda, Y.; Yamada, M.

    1989-07-01

    The confinement and scaling features of the S-1 spheromak have been investigated using magnetic, spectroscopic, and Thomson scattering data in conjunction with numerical modeling. Results from the multipoint Thomson scattering diagnostic shows that the central beta remains constant (/beta//sub to/ /approximately/ 5%) as the plasma current density increases from 0.68--2.1 MA/m/sup 2/. The density is observed to increase slowly over this range, while the central electron temperature increases much more rapidly. Analysis of the global plasma parameters shows a decrease in the volume average beta and energy confinement as the total current is increased. The power balance has been modeled numerically with a 0-D non-equilibrium time-dependent coronal model and is consistent with the experimental observations. 20 refs., 12 figs., 2 tabs.

  9. Regulation of human cerebro-microvascular endothelial baso-lateral adhesion and barrier function by S1P through dual involvement of S1P1 and S1P2 receptors

    PubMed Central

    Wiltshire, Rachael; Nelson, Vicky; Kho, Dan Ting; Angel, Catherine E.; O’Carroll, Simon J.; Graham, E. Scott

    2016-01-01

    Herein we show that S1P rapidly and acutely reduces the focal adhesion strength and barrier tightness of brain endothelial cells. xCELLigence biosensor technology was used to measure focal adhesion, which was reduced by S1P acutely and this response was mediated through both S1P1 and S1P2 receptors. S1P increased secretion of several pro-inflammatory mediators from brain endothelial cells. However, the magnitude of this response was small in comparison to that mediated by TNFα or IL-1β. Furthermore, S1P did not significantly increase cell-surface expression of any key cell adhesion molecules involved in leukocyte recruitment, included ICAM-1 and VCAM-1. Finally, we reveal that S1P acutely and dynamically regulates microvascular endothelial barrier tightness in a manner consistent with regulated rapid opening followed by closing and strengthening of the barrier. We hypothesise that the role of the S1P receptors in this process is not to cause barrier dysfunction, but is related to controlled opening of the endothelial junctions. This was revealed using real-time measurement of barrier integrity using ECIS ZΘ TEER technology and endothelial viability using xCELLigence technology. Finally, we show that these responses do not occur simply though the pharmacology of a single S1P receptor but involves coordinated action of S1P1 and S1P2 receptors. PMID:26813587

  10. Ultraviolet spectroscopy of comet ISON (2012 S1)

    NASA Astrophysics Data System (ADS)

    Weaver, H.; A'Hearn, M.; Feldman, P.; Bodewits, D.; Combi, M.; Dello Russo, N.; McCandliss, S.

    2014-07-01

    We performed ultraviolet (UV) spectroscopy of Comet ISON (C/2012 S1) with the Hubble Space Telescope (HST) to monitor the evolution of CO production with heliocentric distance, search for compositional changes associated with the intense heating episode near perihelion, and measure the D/H ratio. We observed C/ISON with Hubble at four different epochs: May 2.5 (r=3.8 au, Δ=4.3 au), Oct 8.8 (r=1.5 au, Δ= 1.9 au), Oct 21.9 (r=1.23 au, Δ = 1.53 au), and Nov 1.5 (r=1.0 au, Δ =1.2 au). No molecular or atomic emissions were detected in May, but a stringent upper limit on the CO production rate was obtained (Q[CO] ≤ 1.0 × 10^{27} molecules s^{-1}, 3 σ). OH emission was detected during all the later observations and showed strong temporal variations on Nov 1. CO was clearly detected on Oct 21.9 and Nov 1.5, from which we derive CO/H_{2}O ˜0.015. Both atomic carbon and sulfur emissions were detected on Nov 1. No atomic deuterium emission was detected during the attempts to measure it on Nov 1, as the comet's gas production rates were significantly smaller than some early predictions suggested. A lightcurve derived from HST optical imaging observations on Nov 1, contemporaneous with the UV spectroscopy, suggests a nucleus rotational period of ˜10.4 hr, but the range of plausible values is fairly broad.

  11. Growth of ˜5 cm2V-1s-1 mobility, p-type Copper(I) oxide (Cu2O) films by fast atmospheric atomic layer deposition (AALD) at 225°C and below

    NASA Astrophysics Data System (ADS)

    Muñoz-Rojas, D.; Jordan, M.; Yeoh, C.; Marin, A. T.; Kursumovic, A.; Dunlop, L. A.; Iza, D. C.; Chen, A.; Wang, H.; MacManus Driscoll, J. L.

    2012-12-01

    Phase pure, dense Cu2O thin films were grown on glass and polymer substrates at 225°C by rapid atmospheric atomic layer deposition (AALD). Carrier mobilities of 5 cm2V-1s-1 and carrier concentrations of ˜1016 cm-3 were achieved in films of thickness 50 - 120 nm, over a >10 cm2 area. Growth rates were ˜1 nm.min-1 which is two orders of magnitude faster than conventional ALD.. The high mobilities achieved using the atmospheric, low temperature method represent a significant advance for flextronics and flexible solar cells which require growth on plastic substrates.

  12. Possible Dust Models for C/2012 S1

    NASA Astrophysics Data System (ADS)

    Yanamandra-Fisher, P. A.

    2014-12-01

    Comet C/2012 S1 (ISON) provided a great opportunity to study a dynamically new Oort-cloud comet on its initial and only passage through the inner solar system. Contrary to expectations, the comet's activity fluctuated from high through a quiescent phase, and a major outburst days before its perihelion passage, ending in a dramatic race to complete disintegration on perihelion day, 28 November 2013. Amateur observations to professional ground-based, sub-orbital telescopes indicate the various changes of visible factors such as Afrho, a proxy for dust activity, and the measured production rates for water, consistent with the disintegration of the nucleus. Hines et al. (2013; ApJ Lett. 780) detected positive polarization in the inner coma and negative polarization in the outer coma, indicative of a jet, independently confirmed by Li et al. (2013, ApJ Lett., 779). Thermal emission observations of the comet pre-perihelion from NAOJ/Subaru/COMICS, a mid-infrared spectrometer, indicated a body with an equivalent brightness temperature of 265K (Ootsubo et al., 2013, ACM, Helsinki,FI); thermal observations acquired at the NASA/Infrared Telescope Facility (IRTF) with The Aerospace Corporation spectrometer (BASS, PI. R. Russell), before and after the November 12, 2013 outburst observed by the CIOC_ISON amateur network, indicates a brightness temperature of 330K and the presence, albeit weak, of the 11.3-micron crystalline silicate feature (Sitko et al., 2014, LPI abstract 1537). A Monte Carlo comet dust tail model, applied to extract the dust environment parameters of comet C/2012 S1 (ISON) from both Earth-based and Solar and Heliospheric Observatory (SOHO) calibrated observations, performed from about 6 AU (inbound), to right after perihelion passage, when just a small portion of the original comet nucleus survived in the form of a cloud of tiny particles, indicates that particles underwent disintegration and fragmentation (Moreno et al., 2014, ApJ Lett., 791). Ongoing work

  13. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human

    PubMed Central

    Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-01-01

    The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3–4 compared to those with 0–2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target. PMID:27562371

  14. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.

    PubMed

    Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-01-01

    The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target. PMID:27562371

  15. Photometry of distant active comet C/2010 S1 (LINEAR)

    NASA Astrophysics Data System (ADS)

    Shubina, O.; Kulyk, I.; Korsun, P.; Romanjuk, Ya.

    2014-12-01

    We present the results of photometric observations of a dynamically new comet C/2010 S1 (LINEAR), conducted on June 18, 2012. The comet demonstrated a considerable level of physical activity at a heliocentric distance of 6.3 AU. The brightness, measured under a phase angle of 8.9 degrees, was equal to 14.55^{m}±0.06^{m} and 14.21^{m}±0.04^{m} in V- and R-bands, respectively. The brightness distribution over the coma was found to be inversely proportional to the projected onto the sky plane nucleocentric distance, with a slope of approximately -1. Therefore, the calculated Afρ parameter, approximately 8400 cm and 8200 cm for V and R filters, respectively, was used to estimate the dust production rate. Assuming a steady outflow of dust particles from the nucleus, the dust production rate was estimated to be between 20 and 60 kg/s, depending on the assumed value of the grain's albedo. The V-R colour index obtained from the near-nucleus region of the coma is in agreement with the solar V-R colour index, and does not indicate significant reddening of the reflected solar radiation in the spectral region of 540-683 nm.

  16. Outgassing and chemical evolution of C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Dello Russo, Neil; Vervack, Ronald J.; Kawakita, Hideyo; Cochran, Anita; McKay, Adam J.; Harris, Walter M.; Weaver, Harold A.; Lisse, Carey M.; DiSanti, Michael A.; Kobayashi, Hitomi; Biver, Nicolas; Bockelée-Morvan, Dominique; Crovisier, Jacques; Opitom, Cyrielle; Jehin, Emmanuel

    2015-11-01

    Volatile production rates, relative abundances, rotational temperatures, and spatial distributions in the coma were measured in C/2012 S1 (ISON) using long-slit high-dispersion (λ/Δλ ~ 25,000) infrared spectroscopy as part of a worldwide observing campaign. Spectra were obtained on UT 2013 October 26 and 28 with NIRSPEC at the W. M. Keck Observatory, and UT 2013 November 19 and 20 with CSHELL at the NASA IRTF. H2O was detected on all dates, with production rates increasing by about a factor of 40 between October 26 (Rh = 1.12 AU) and November 20 (Rh = 0.43 AU). Short-term variability of H2O was also seen as the production rate increased by nearly a factor of two during observations obtained over a period of about six hours on November 19. C2H6, CH3OH and CH4 abundances were slightly depleted relative to H2O in ISON compared to mean values for comets measured at infrared wavelengths. On the November dates, C2H2, HCN and OCS abundances relative to H2O appear to be close to the range of mean values, whereas H2CO and NH3 were significantly enhanced. We will compare derived chemical abundances in ISON to other comets measured with infrared spectroscopy.

  17. Sphingosine 1-Phosphate (S1P) Receptor Agonists Mediate Pro-fibrotic Responses in Normal Human Lung Fibroblasts via S1P2 and S1P3 Receptors and Smad-independent Signaling

    PubMed Central

    Sobel, Katrin; Menyhart, Katalin; Killer, Nina; Renault, Bérengère; Bauer, Yasmina; Studer, Rolf; Steiner, Beat; Bolli, Martin H.; Nayler, Oliver; Gatfield, John

    2013-01-01

    Synthetic sphingosine 1-phosphate receptor 1 modulators constitute a new class of drugs for the treatment of autoimmune diseases. Sphingosine 1-phosphate (S1P) signaling, however, is also involved in the development of fibrosis. Using normal human lung fibroblasts, we investigated the induction of fibrotic responses by the S1P receptor (S1PR) agonists S1P, FTY720-P, ponesimod, and SEW2871 and compared them with the responses induced by the known fibrotic mediator TGF-β1. In contrast to TGF-β1, S1PR agonists did not induce expression of the myofibroblast marker α-smooth muscle actin. However, TGF-β1, S1P, and FTY720-P caused robust stimulation of extracellular matrix (ECM) synthesis and increased pro-fibrotic marker gene expression including connective tissue growth factor. Ponesimod showed limited and SEW2871 showed no pro-fibrotic potential in these readouts. Analysis of pro-fibrotic signaling pathways showed that in contrast to TGF-β1, S1PR agonists did not activate Smad2/3 signaling but rather activated PI3K/Akt and ERK1/2 signaling to induce ECM synthesis. The strong induction of ECM synthesis by the nonselective agonists S1P and FTY720-P was due to the stimulation of S1P2 and S1P3 receptors, whereas the weaker induction of ECM synthesis at high concentrations of ponesimod was due to a low potency activation of S1P3 receptors. Finally, in normal human lung fibroblast-derived myofibroblasts that were generated by TGF-β1 pretreatment, S1P and FTY720-P were effective stimulators of ECM synthesis, whereas ponesimod was inactive, because of the down-regulation of S1P3R expression in myofibroblasts. These data demonstrate that S1PR agonists are pro-fibrotic via S1P2R and S1P3R stimulation using Smad-independent pathways. PMID:23589284

  18. Search for ammonia in comet C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Faggi, S.; Codella, C.; Tozzi, G.; Comoretto, G.; Crovisier, J.; Nesti, R.; Panella, D.; Boissier, J.; Bolli, P.; Brucato, J.; Massi, F.; Tofani, G.

    2014-07-01

    Comets are pristine bodies of the Solar System and their studies can give precious hints on the formation of the Solar System itself. New comets, coming form the Oort Colud at their first passage close to the Sun, are particularly important, because they are not differentiated by the Solar radiation and they are supposed to have a large quantity of organic matter close to the surface. Here we report the results of a search for NH_3(1,1) emission at 23.7 GHz in comet C/2012 S1 ISON using a new dual-feed K-band receiver mounted on the Medicina 32-m antenna. We observed the comet once close to its perihelion, from 2013 Nov. 25 to Nov. 28, when its heliocentric distance changed from 0.25 au to 0.03 au. We integrated about 6 hrs per day, obtaining high-spectral-resolution (1 km/s) spectra with a typical rms noise of 10 mK. Such sensitivity allowed us to derive an upper limit of Q(NH_3) of about 2.5 ×10^{29} mol/s on November 26. This upper limit would correspond to a Q(H_2O) of about 2.5 ×10^{31} mol/s, assuming the typical Q(H_2O)/Q(NH_3) ratio of 100. These findings confirm that no significant Q(H_2O) enhancement happened near the perihelion, consistent with a definitive decrease of molecules production rate.

  19. Ultraviolet Observations Of C/2012 S1 (ISON) By MAVEN

    NASA Astrophysics Data System (ADS)

    Crismani, Matteo; Schneider, N.; Stewart, I.; Combi, M.; Fougere, N.

    2013-10-01

    On its journey to Mars, MAVEN has been serendipitously positioned to study the anticipated sungrazing comet C/2012 S1(ISON) and offers important scientific observations. The MAVEN mission is the first to attempt to understand the evolution of the Martian atmosphere by determining the effects of atmospheric loss to space. The IUVS instrument has two large field of regard(55x11 and 24x11 degrees) and observes in the mid and far ultraviolet (115-340 nm). It was designed to be able to map the atmosphere in several neutral and some ionized species. These performance characteristics make IUVS ideal to study ISON, as it can take both two dimensional spatial scans as well as spectral data. Tentative plans indicate the comet can be acquired on Dec 8th, assuming that the comet survives the near sun encounter. If observations prove possible, IUVS will be able to study ISON shortly after perihelion, and from a different vantage point from Earth. Science goals include UV observations of D/H, morphology & time evolution of the hydrogen coma and UV spectroscopy of the inner coma. IUVS can potentially make a major contribution to the international community by measuring D/H, thus contributing to our understanding of the origin of Earth’s water. IUVS will also make MUV and FUV observations of molecular species in the inner coma, valuable for understanding the chemical evolution of cometary molecular gases. The poster will present provisional observation plans as well as simulated spectra and spatial profiles. We welcome input from the community on these plans, in the spirit of maximizing the scientific return of the international campaign. The work has been supported by the MAVEN project and NASA Planetary Atmospheres grant NNX09AB59G.

  20. WILL COMET ISON (C/2012 S1) SURVIVE PERIHELION?

    SciTech Connect

    Knight, Matthew M.; Walsh, Kevin J.

    2013-10-10

    On 2013 November 28 Comet ISON (C/2012 S1) will pass by the Sun with a perihelion distance of 2.7 solar radii. Understanding the possible outcomes for the comet's response to such a close passage by the Sun is important for planning observational campaigns and for inferring ISON's physical properties. We present new numerical simulations and interpret them in context with the historical track record of comet disruptions and of sungrazing comet behavior. Historical data suggest that sizes below ∼200 m are susceptible to destruction by sublimation driven mass loss, while we find that for ISON's perihelion distance, densities lower than 0.1 g cm{sup –3} are required to tidally disrupt a retrograde or non-spinning body. Such low densities are substantially below the range of the best-determined comet nucleus densities, though dynamically new comets such as ISON have few measurements of physical properties. Disruption may occur for prograde rotation at densities up to 0.7 g cm{sup –3}, with the chances of disruption increasing for lower density, faster prograde rotation, and increasing elongation of the nucleus. Given current constraints on ISON's nucleus properties and the typically determined values for these properties among all comets, we find tidal disruption to be unlikely unless other factors (e.g., spin-up via torquing) affect ISON substantially. Whether or not disruption occurs, the largest remnant must be big enough to survive subsequent mass loss due to sublimation in order for ISON to remain a viable comet well after perihelion.

  1. Gravitational dynamics in s+1+1 dimensions

    SciTech Connect

    Gergely, Laszlo A.; Kovacs, Zoltan

    2005-09-15

    We present the concomitant decomposition of an (s+2)-dimensional space-time both with respect to a timelike and a spacelike direction. The formalism we develop is suited for the study of the initial value problem and for canonical gravitational dynamics in braneworld scenarios. The bulk metric is replaced by two sets of variables. The first set consists of one tensorial (the induced metric g{sub ij}), one vectorial (M{sup i}) and one scalar (M) dynamical quantity, all defined on the s space. Their time evolutions are related to the second fundamental form (the extrinsic curvature K{sub ij}), the normal fundamental form (K{sup i}) and normal fundamental scalar (K), respectively. The nondynamical set of variables is given by the lapse function and the shift vector, which however has one component less. The missing component is due to the externally imposed constraint, which states that physical trajectories are confined to the (s+1)-dimensional brane. The pair of dynamical variables (g{sub ij}, K{sub ij}), well known from the Arnowitt-Deser-Misner decomposition is supplemented by the pairs (M{sup i}, K{sup i}) and (M, K) due to the bulk curvature. We give all projections of the junction condition across the brane and prove that for a perfect fluid brane neither of the dynamical variables has jump across the brane. Finally we complete the set of equations needed for gravitational dynamics by deriving the evolution equations of K{sub ij}, K{sup i} and K on a brane with arbitrary matter.

  2. A role of the sphingosine-1-phosphate (S1P)–S1P receptor 2 pathway in epithelial defense against cancer (EDAC)

    PubMed Central

    Yamamoto, Sayaka; Yako, Yuta; Fujioka, Yoichiro; Kajita, Mihoko; Kameyama, Takeshi; Kon, Shunsuke; Ishikawa, Susumu; Ohba, Yusuke; Ohno, Yusuke; Kihara, Akio; Fujita, Yasuyuki

    2016-01-01

    At the initial step of carcinogenesis, transformation occurs in single cells within epithelia, where the newly emerging transformed cells are surrounded by normal epithelial cells. A recent study revealed that normal epithelial cells have an ability to sense and actively eliminate the neighboring transformed cells, a process named epithelial defense against cancer (EDAC). However, the molecular mechanism of this tumor-suppressive activity is largely unknown. In this study, we investigated a role for the sphingosine-1-phosphate (S1P)–S1P receptor 2 (S1PR2) pathway in EDAC. First, we show that addition of the S1PR2 inhibitor significantly suppresses apical extrusion of RasV12-transformed cells that are surrounded by normal cells. In addition, knockdown of S1PR2 in normal cells induces the same effect, indicating that S1PR2 in the surrounding normal cells plays a positive role in the apical elimination of the transformed cells. Of importance, not endogenous S1P but exogenous S1P is involved in this process. By using FRET analyses, we demonstrate that S1PR2 mediates Rho activation in normal cells neighboring RasV12-transformed cells, thereby promoting accumulation of filamin, a crucial regulator of EDAC. Collectively these data indicate that S1P is a key extrinsic factor that affects the outcome of cell competition between normal and transformed epithelial cells. PMID:26631556

  3. Mg dopant in Cu2SnSe3: An n-type former and a promoter of electrical mobility up to 387 cm2 V-1 s-1

    NASA Astrophysics Data System (ADS)

    Kuo, Dong-Hau; Wubet, Walelign

    2014-10-01

    Mg-doped Cu2SnSe3 bulk materials with the (Cu2-xMgx)SnSe3 (Mg-x-CTSe) formula at x=0, 0.05, 0.1, 0.15, and 0.2 were prepared at 550 °C for 2 h with soluble sintering aids of Sb2S3 and Te. Defect chemistry was studied by measuring structural and electrical properties of Mg-doped Cu2SnSe3 as a function of dopant concentration. Mg-x-CTSe pellets show p-type at x=0, 0.05 and 0.1 and n-type at x=0.15 and 0.2. The low hole concentration of 3.2×1017 cm-3 and high mobility of 387 cm2 V-1 s-1 were obtained for (Cu2-xMgx)SnSe3 bulks at x=0.1 (5% Mg) as compared to 2.2×1018 cm-3 and 91 cm2 V-1 s-1 for the undoped one. The explanation based upon the Mg-to-Cu antisite donor defect for the changes in electrical property was declared. A high Mg content for Mg-x-CTSe at x≥0.1 can lead to the formation of second phases. The study in bulk Mg-x-CTSe has been based upon defect states and is consistent and supported by the data of structural and electrical properties.

  4. Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2

    PubMed Central

    Patmanathan, Sathya Narayanan; Johnson, Steven P.; Lai, Sook Ling; Panja Bernam, Suthashini; Lopes, Victor; Wei, Wenbin; Ibrahim, Maha Hafez; Torta, Federico; Narayanaswamy, Pradeep; Wenk, Markus R.; Herr, Deron R.; Murray, Paul G.; Yap, Lee Fah; Paterson, Ian C.

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target. PMID:27160553

  5. Ligand-binding pocket shape differences between S1P1 and S1P3 determine efficiency of chemical probe identification by uHTS

    PubMed Central

    Schürer, Stephan C.; Brown, Steven J.; Cabrera, Pedro Gonzales; Schaeffer, Marie-Therese; Chapman, Jacqueline; Jo, Euijung; Chase, Peter; Spicer, Tim; Hodder, Peter; Rosen, Hugh

    2008-01-01

    We have studied the Sphingosine 1-phosphate (S1P) receptor system to better understand why certain molecular targets within a closely related family are much more tractable when identifying compelling chemical leads. Five medically important G protein-coupled receptors for S1P regulate heart rate, coronary artery caliber, endothelial barrier integrity, and lymphocyte trafficking. Selective S1P receptor agonist probes would be of great utility to study receptor subtype-specific function. Through systematic screening of the same libraries, we identified novel selective agonists chemotypes for each of the S1P1 and S1P3 receptors. uHTS for S1P1 was more effective than for S1P3, with many selective, low nanomolar hits of proven mechanism emerging for. Receptor structure modeling and ligand docking reveal differences between the receptor binding pockets, which are the basis for sub-type selectivity. Novel selective agonists interact primarily in the hydrophobic pocket of the receptor in the absence of head-group interactions. Chemistry-space and shape-based analysis of the screening libraries in combination with the binding models explain the observed differential hit rates and enhanced efficiency for lead discovery for S1P1 vs. S1P3 in this closely related receptor family. PMID:18590333

  6. [Stable and efficient expression of hepatitis B virus S antigen and preS1 epitope fusion protein (S/preS1) in CHO cells].

    PubMed

    Yang, Zhenxi; Li, Shichong; Liu, Hong; Zhang, Miao; Ye, Lingling; Wu, Yanzhuo; Xu, Mingbo; Chen, Zhaolie

    2013-12-01

    Hepatitis B surface antigen (HBsAg) carrying preS sequences could be an ideal candidate for a new hepatitis B virus (HBV) vaccine with higher efficacy. Here we report the success in achieving efficient and stable expression of hepatitis B virus S antigen and preS1 epitope fusion protein (S/preS1) in CHO cells. The HMRCHEF53u/Neo-S/preS1 expression vector carrying S/preS1 gene was constructed and transfected into CHO-S cells. A stable and high-expression CHO cell line, named 10G6, was selected by ELISA and limiting dilution analysis. Western blotting analysis showed S/preS1 expressed from 10G6 cells possessed both S and preS1 antigenicity. 10G6 cells displayed characters of favorable growth and stable S/preS1 expression in repeated batch cultures as evaluated by viable cell density, viability and S/preS1 concentration. And cultivation of 10G6 cells in fed-batch mode resulted in S/preS1 production at 17-20 mg/L with viable cell density at 7 x 10(6)-10 x 10(6) cells/mL. PMID:24660628

  7. Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2.

    PubMed

    Patmanathan, Sathya Narayanan; Johnson, Steven P; Lai, Sook Ling; Panja Bernam, Suthashini; Lopes, Victor; Wei, Wenbin; Ibrahim, Maha Hafez; Torta, Federico; Narayanaswamy, Pradeep; Wenk, Markus R; Herr, Deron R; Murray, Paul G; Yap, Lee Fah; Paterson, Ian C

    2016-01-01

    Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target. PMID:27160553

  8. Molecular Dynamics Simulations to Investigate the Influences of Amino Acid Mutations on Protein Three-Dimensional Structures of Cytochrome P450 2D6.1, 2, 10, 14A, 51, and 62

    PubMed Central

    Watanabe, Yurie; Hiratsuka, Masahiro; Yamaotsu, Noriyuki; Hirono, Shuichi; Manabe, Noriyoshi; Takahashi, Ohgi; Oda, Akifumi

    2016-01-01

    Many natural mutants of the drug metabolizing enzyme cytochrome P450 (CYP) 2D6 have been reported. Because the enzymatic activities of many mutants are different from that of the wild type, the genetic polymorphism of CYP2D6 plays an important role in drug metabolism. In this study, the molecular dynamics simulations of the wild type and mutants of CYP2D6, CYP2D6.1, 2, 10, 14A, 51, and 62 were performed, and the predictions of static and dynamic structures within them were conducted. In the mutant CYP2D6.10, 14A, and 61, dynamic properties of the F-G loop, which is one of the components of the active site access channel of CYP2D6, were different from that of the wild type. The F-G loop acted as the “hatch” of the channel, which was closed in those mutants. The structure of CYP2D6.51 was not converged by the simulation, which indicated that the three-dimensional structure of CYP2D6.51 was largely different from that of the wild type. In addition, the intramolecular interaction network of CYP2D6.10, 14A, and 61 was different from that of the wild type, and it is considered that these structural changes are the reason for the decrease or loss of enzymatic activities. On the other hand, the static and dynamic properties of CYP2D6.2, whose activity was normal, were not considerably different from those of the wild type. PMID:27046024

  9. Genetic characterization of three qnrS1-harbouring multidrug-resistance plasmids and qnrS1-containing transposons circulating in Ho Chi Minh City, Vietnam

    PubMed Central

    Le, Vien; Nhu, Nguyen Thi Khanh; Cerdeno-Tarraga, Ana; Campbell, James I.; Tuyen, Ha Thanh; Nhu, Tran Do Hoang; Tam, Pham Thi Thanh; Schultsz, Constance; Thwaites, Guy; Thomson, Nicholas R.

    2015-01-01

    Plasmid-mediated quinolone resistance (PMQR) refers to a family of closely related genes that confer decreased susceptibility to fluoroquinolones. PMQR genes are generally associated with integrons and/or plasmids that carry additional antimicrobial resistance genes active against a range of antimicrobials. In Ho Chi Minh City (HCMC), Vietnam, we have previously shown a high frequency of PMQR genes within commensal Enterobacteriaceae. However, there are limited available sequence data detailing the genetic context in which the PMQR genes reside, and a lack of understanding of how these genes spread across the Enterobacteriaceae. Here, we aimed to determine the genetic background facilitating the spread and maintenance of qnrS1, the dominant PMQR gene circulating in HCMC. We sequenced three qnrS1-carrying plasmids in their entirety to understand the genetic context of these qnrS1-embedded plasmids and also the association of qnrS1-mediated quinolone resistance with other antimicrobial resistance phenotypes. Annotation of the three qnrS1-containing plasmids revealed a qnrS1-containing transposon with a closely related structure. We screened 112 qnrS1-positive commensal Enterobacteriaceae isolated in the community and in a hospital in HCMC to detect the common transposon structure. We found the same transposon structure to be present in 71.4 % (45/63) of qnrS1-positive hospital isolates and in 36.7 % (18/49) of qnrS1-positive isolates from the community. The resulting sequence analysis of the qnrS1 environment suggested that qnrS1 genes are widely distributed and are mobilized on elements with a common genetic background. Our data add additional insight into mechanisms that facilitate resistance to multiple antimicrobials in Gram-negative bacteria in Vietnam. PMID:26272054

  10. The S1P/S1PR2 axis regulates early airway T cell infiltration in murine mast cell-dependent acute allergic responses

    PubMed Central

    Oskeritzian, Carole A.; Hait, Nitai C.; Wedman, Piper; Chumanevich, Alena; Kolawole, Elizabeth M.; Price, Megan M.; Falanga, Yves T.; Harikumar, Kuzhuvelil B.; Ryan, John J.; Milstien, Sheldon; Sabbadini, Roger; Spiegel, Sarah

    2014-01-01

    Background Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid produced by mast cells (MC) upon cross-linking of their high affinity receptors for IgE by antigen (Ag) that can amplify MC responses by binding to its S1P receptors. Acute MC-dependent allergic reaction can lead to systemic shock but the early events of its development in lung tissues have not been investigated, and S1P functions in the onset of allergic processes remain to be examined. Objective We used a highly specific neutralizing anti-S1P antibody (mAb) and an S1P receptor 2 (S1PR2) antagonist, JTE-013, to study S1P and S1PR2 signaling contributions to MC- and IgE-dependent airway allergic responses in mice within minutes after Ag challenge. Methods Allergic reaction was triggered by a single intraperitoneal (i.p.) dose of Ag in sensitized mice pre-treated i.p. with anti-S1P or isotype control mAb, or JTE-013 or vehicle prior to Ag challenge. Results Kinetics experiments revealed early pulmonary infiltration of mostly T cells around blood vessels of sensitized mice 20 minutes post-Ag exposure. Pre-treatment with anti-S1P mAb inhibited in vitro MC activation, as well as in vivo development of airway infiltration and MC activation, reducing serum levels of histamine, cytokines and the chemokines MCP-1/CCL2, MIP-1α/CCL3 and RANTES/CCL5. S1PR2 antagonism or deficiency, or MC deficiency recapitulated these results. Both in vitro and in vivo experiments demonstrated MC S1PR2 dependency for chemokine release and the necessity for signal transducer and activator of transcription 3 (Stat3) activation. Conclusion Activation of S1PR2 by S1P and downstream Stat3 signaling in MC regulate early T cell recruitment to antigen-challenged lungs by chemokine production. PMID:25512083

  11. Systematic Study of Rayleigh-Taylor Growth in Directly Driven Plastic Targets in a Laser-Intensity Range from ~2 x 10^14 to ~1.5 x 10^15 W/cm^2

    SciTech Connect

    Smalyuk, V.A.; Hu, S.X.; Goncharov, V.N.; Meyerhofer, D.D.; Sangster, T.C.; Stoeckl, C.; Yaakobi, B.

    2008-09-05

    Direct-drive, Rayleigh–Taylor (RT) growth experiments were performed using planar plastic targets on the OMEGA Laser Facility [T. R. Boehly et al., Opt. Commun. 133, 495 (1997)] at laser intensities between ~2 x 10^14 and ~1.5 x 10^15 W/cm^2. The primary purpose of the experiments was to test fundamental physics in hydrocodes at the range of drive intensities relevant to ignition designs. The target acceleration was measured with a streak camera using side-on, x-ray radiography, while RT growth was measured with a framing camera using face-on radiography. In a laser-intensity range from 2 to 5 x 10^14 W/cm^2, the measured RT growth agrees well with two-dimensional simulations, based on a local model of thermal-electron transport. The RT growth at drive intensities above ~1.0 x 10^15 W/cm^2 was strongly stabilized compared to the local model predictions. The experiments demonstrate that standard simulations, based on a local model of electron thermal transport, break down at peak intensities of ignition designs, although they work well at lower intensities. These results also imply that direct-drive ignition targets are significantly more stable than previously calculated using local electron-transport models at peak intensities of ignition designs. The preheating effects by nonlocal electron transport and hot electrons were identified as some of the stabilizing mechanisms.

  12. HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications

    PubMed Central

    Levkau, Bodo

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid contained in High-density lipoproteins (HDL) and has drawn considerable attention in the lipoprotein field as numerous studies have demonstrated its contribution to several functions inherent to HDL. Some of them are partly and some entirely due to the S1P contained in HDL (HDL-S1P). Despite the presence of over 1000 different lipids in HDL, S1P stands out as it possesses its own cell surface receptors through which it exercises key physiological functions. Most of the S1P in human plasma is associated with HDL, and the amount of HDL-S1P influences the quality and quantity of HDL-dependent functions. The main binding partner of S1P in HDL is apolipoprotein M but others may also exist particularly under conditions of acute S1P elevations. HDL not only exercise functions through their S1P content but have also an impact on genuine S1P signaling by influencing S1P bioactivity and receptor presentation. HDL-S1P content is altered in human diseases such as atherosclerosis, coronary artery disease, myocardial infarction, renal insufficiency and diabetes mellitus. Low HDL-S1P has also been linked to impaired HDL functions associated with these disorders. Although the pathophysiological and molecular reasons for such disease-associated shifts in HDL-S1P are little understood, there have been successful approaches to circumvent their adverse implications by pharmacologically increasing HDL-S1P as means to improve HDL function. This mini-review will cover the current understanding of the contribution of HDL-S1P to physiological HDL function, its alteration in disease and ways for its restoration to correct HDL dysfunction. PMID:26539121

  13. 26 CFR 31.3121(s)-1 - Concurrent employment by related corporations with common paymaster.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... with common paymaster. 31.3121(s)-1 Section 31.3121(s)-1 Internal Revenue INTERNAL REVENUE SERVICE... Revenue Code of 1954) General Provisions § 31.3121(s)-1 Concurrent employment by related corporations with... this section. Section 3121(s) and this section apply only to remuneration disbursed in the form...

  14. 26 CFR 1.6050S-1 - Information reporting for qualified tuition and related expenses.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 13 2012-04-01 2012-04-01 false Information reporting for qualified tuition and related expenses. 1.6050S-1 Section 1.6050S-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Information Returns § 1.6050S-1 Information reporting for...

  15. The phylogeny of C/S1 bZIP transcription factors reveals a shared algal ancestry and the pre-angiosperm translational regulation of S1 transcripts.

    PubMed

    Peviani, Alessia; Lastdrager, Jeroen; Hanson, Johannes; Snel, Berend

    2016-01-01

    Basic leucine zippers (bZIPs) form a large plant transcription factor family. C and S1 bZIP groups can heterodimerize, fulfilling crucial roles in seed development and stress response. S1 sequences also harbor a unique regulatory mechanism, termed Sucrose-Induced Repression of Translation (SIRT). The conservation of both C/S1 bZIP interactions and SIRT remains poorly characterized in non-model species, leaving their evolutionary origin uncertain and limiting crop research. In this work, we explored recently published plant sequencing data to establish a detailed phylogeny of C and S1 bZIPs, investigating their intertwined role in plant evolution, and the origin of SIRT. Our analyses clarified C and S1 bZIP orthology relationships in angiosperms, and identified S1 sequences in gymnosperms. We experimentally showed that the gymnosperm orthologs are regulated by SIRT, tracing back the origin of this unique regulatory mechanism to the ancestor of seed plants. Additionally, we discovered an earlier S ortholog in the charophyte algae Klebsormidium flaccidum, together with a C ortholog. This suggests that C and S groups originated by duplication from a single algal proto-C/S ancestor. Based on our observations, we propose a model wherein the C/S1 bZIP dimer network evolved in seed plants from pre-existing C/S bZIP interactions. PMID:27457880

  16. The phylogeny of C/S1 bZIP transcription factors reveals a shared algal ancestry and the pre-angiosperm translational regulation of S1 transcripts

    PubMed Central

    Peviani, Alessia; Lastdrager, Jeroen; Hanson, Johannes; Snel, Berend

    2016-01-01

    Basic leucine zippers (bZIPs) form a large plant transcription factor family. C and S1 bZIP groups can heterodimerize, fulfilling crucial roles in seed development and stress response. S1 sequences also harbor a unique regulatory mechanism, termed Sucrose-Induced Repression of Translation (SIRT). The conservation of both C/S1 bZIP interactions and SIRT remains poorly characterized in non-model species, leaving their evolutionary origin uncertain and limiting crop research. In this work, we explored recently published plant sequencing data to establish a detailed phylogeny of C and S1 bZIPs, investigating their intertwined role in plant evolution, and the origin of SIRT. Our analyses clarified C and S1 bZIP orthology relationships in angiosperms, and identified S1 sequences in gymnosperms. We experimentally showed that the gymnosperm orthologs are regulated by SIRT, tracing back the origin of this unique regulatory mechanism to the ancestor of seed plants. Additionally, we discovered an earlier S ortholog in the charophyte algae Klebsormidium flaccidum, together with a C ortholog. This suggests that C and S groups originated by duplication from a single algal proto-C/S ancestor. Based on our observations, we propose a model wherein the C/S1 bZIP dimer network evolved in seed plants from pre-existing C/S bZIP interactions. PMID:27457880

  17. The Clinically-tested S1P Receptor Agonists, FTY720 and BAF312, Demonstrate Subtype-Specific Bradycardia (S1P1) and Hypertension (S1P3) in Rat

    PubMed Central

    Fryer, Ryan M.; Muthukumarana, Akalushi; Harrison, Paul C.; Nodop Mazurek, Suzanne; Chen, Rong Rhonda; Harrington, Kyle E.; Dinallo, Roger M.; Horan, Joshua C.; Patnaude, Lori; Modis, Louise K.; Reinhart, Glenn A.

    2012-01-01

    Sphingosine-1-phospate (S1P) and S1P receptor agonists elicit mechanism-based effects on cardiovascular function in vivo. Indeed, FTY720 (non-selective S1PX receptor agonist) produces modest hypertension in patients (2–3 mmHg in 1-yr trial) as well as acute bradycardia independent of changes in blood pressure. However, the precise receptor subtypes responsible is controversial, likely dependent upon the cardiovascular response in question (e.g. bradycardia, hypertension), and perhaps even species-dependent since functional differences in rodent, rabbit, and human have been suggested. Thus, we characterized the S1P receptor subtype specificity for each compound in vitro and, in vivo, the cardiovascular effects of FTY720 and the more selective S1P1,5 agonist, BAF312, were tested during acute i.v. infusion in anesthetized rats and after oral administration for 10 days in telemetry-instrumented conscious rats. Acute i.v. infusion of FTY720 (0.1, 0.3, 1.0 mg/kg/20 min) or BAF312 (0.5, 1.5, 5.0 mg/kg/20 min) elicited acute bradycardia in anesthetized rats demonstrating an S1P1 mediated mechanism-of-action. However, while FTY720 (0.5, 1.5, 5.0 mg/kg/d) elicited dose-dependent hypertension after multiple days of oral administration in rat at clinically relevant plasma concentrations (24-hr mean blood pressure = 8.4, 12.8, 16.2 mmHg above baseline vs. 3 mmHg in vehicle controls), BAF312 (0.3, 3.0, 30.0 mg/kg/d) had no significant effect on blood pressure at any dose tested suggesting that hypertension produced by FTY720 is mediated S1P3 receptors. In summary, in vitro selectivity results in combination with studies performed in anesthetized and conscious rats administered two clinically tested S1P agonists, FTY720 or BAF312, suggest that S1P1 receptors mediate bradycardia while hypertension is mediated by S1P3 receptor activation. PMID:23285242

  18. The clinically-tested S1P receptor agonists, FTY720 and BAF312, demonstrate subtype-specific bradycardia (S1P₁) and hypertension (S1P₃) in rat.

    PubMed

    Fryer, Ryan M; Muthukumarana, Akalushi; Harrison, Paul C; Nodop Mazurek, Suzanne; Chen, Rong Rhonda; Harrington, Kyle E; Dinallo, Roger M; Horan, Joshua C; Patnaude, Lori; Modis, Louise K; Reinhart, Glenn A

    2012-01-01

    Sphingosine-1-phospate (S1P) and S1P receptor agonists elicit mechanism-based effects on cardiovascular function in vivo. Indeed, FTY720 (non-selective S1P(X) receptor agonist) produces modest hypertension in patients (2-3 mmHg in 1-yr trial) as well as acute bradycardia independent of changes in blood pressure. However, the precise receptor subtypes responsible is controversial, likely dependent upon the cardiovascular response in question (e.g. bradycardia, hypertension), and perhaps even species-dependent since functional differences in rodent, rabbit, and human have been suggested. Thus, we characterized the S1P receptor subtype specificity for each compound in vitro and, in vivo, the cardiovascular effects of FTY720 and the more selective S1P₁,₅ agonist, BAF312, were tested during acute i.v. infusion in anesthetized rats and after oral administration for 10 days in telemetry-instrumented conscious rats. Acute i.v. infusion of FTY720 (0.1, 0.3, 1.0 mg/kg/20 min) or BAF312 (0.5, 1.5, 5.0 mg/kg/20 min) elicited acute bradycardia in anesthetized rats demonstrating an S1P₁ mediated mechanism-of-action. However, while FTY720 (0.5, 1.5, 5.0 mg/kg/d) elicited dose-dependent hypertension after multiple days of oral administration in rat at clinically relevant plasma concentrations (24-hr mean blood pressure = 8.4, 12.8, 16.2 mmHg above baseline vs. 3 mmHg in vehicle controls), BAF312 (0.3, 3.0, 30.0 mg/kg/d) had no significant effect on blood pressure at any dose tested suggesting that hypertension produced by FTY720 is mediated S1P₃ receptors. In summary, in vitro selectivity results in combination with studies performed in anesthetized and conscious rats administered two clinically tested S1P agonists, FTY720 or BAF312, suggest that S1P₁ receptors mediate bradycardia while hypertension is mediated by S1P₃ receptor activation. PMID:23285242

  19. A randomized phase II study of S-1 plus oral leucovorin versus S-1 monotherapy in patients with gemcitabine-refractory advanced pancreatic cancer†

    PubMed Central

    Ueno, M.; Okusaka, T.; Omuro, Y.; Isayama, H.; Fukutomi, A.; Ikeda, M.; Mizuno, N.; Fukuzawa, K.; Furukawa, M.; Iguchi, H.; Sugimori, K.; Furuse, J.; Shimada, K.; Ioka, T.; Nakamori, S.; Baba, H.; Komatsu, Y.; Takeuchi, M.; Hyodo, I.; Boku, N.

    2016-01-01

    Background We evaluated the efficacy and toxicity of adding oral leucovorin (LV) to S-1 when compared with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer (PC). Patients and methods Gemcitabine-refractory PC patients were randomly assigned in a 1:1 ratio to receive S-1 at 40, 50, or 60 mg according to body surface area plus LV 25 mg, both given orally twice daily for 1 week, repeated every 2 weeks (SL group), or S-1 monotherapy at the same dose as the SL group for 4 weeks, repeated every 6 weeks (S-1 group). The primary end point was progression-free survival (PFS). Results Among 142 patients enrolled, 140 were eligible for efficacy assessment (SL: n = 69 and S-1: n = 71). PFS was significantly longer in the SL group than in the S-1 group [median PFS, 3.8 versus 2.7 months; hazard ratio (HR), 0.56; 95% confidence interval (CI), 0.37–0.85; P = 0.003]). The disease control rate was significantly higher in the SL group than in the S-1 group (91% versus 72%; P = 0.004). Overall survival (OS) was similar in both groups (median OS, 6.3 versus 6.1 months; HR, 0.82; 95% CI, 0.54–1.22; P = 0.463). After adjusting for patient background factors in a multivariate analysis, OS tended to be better in the SL group (HR, 0.71; 95% CI, 0.47–1.07; P = 0.099). Both treatments were well tolerated, although gastrointestinal toxicities were slightly more severe in the SL group. Conclusion The addition of LV to S-1 significantly improved PFS in patients with gemcitabine-refractory advanced PC, and a phase III trial has been initiated in a similar setting. Clinical trials number Japan Pharmaceutical Information Center: JapicCTI-111554. PMID:26681680

  20. S1P lyase in skeletal muscle regeneration and satellite cell activation: Exposing the hidden lyase☆

    PubMed Central

    Saba, Julie D.; de la Garza-Rodea, Anabel S.

    2013-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid whose actions are essential for many physiological processes including angiogenesis, lymphocyte trafficking and development. In addition, S1P serves asamuscle trophic factor that enables efficient muscle regeneration. This is due in part to S1P's ability to activate quiescent muscle stem cells called satellite cells (SCs) that are needed for muscle repair. However, the molecular mechanism by which S1P activates SCs has not been well understood. Further, strategies for harnessing S1P signaling to recruit SCs for therapeutic benefit have been lacking. S1P is irreversibly catabolized by S1P lyase (SPL), a highly conserved enzyme that catalyzes the cleavage of S1P at carbon bond C2–3, resulting in formation of hexadecenal and ethanolamine-phosphate. SPL enhances apoptosis through substrate- and product-dependent events, thereby regulating cellular responses to chemotherapy, radiation and ischemia. SPL is undetectable in resting murine skeletal muscle. However, we recently found that SPL is dynamically upregulated in skeletal muscle after injury. SPL upregulation occurred in the context of a tightly orchestrated genetic program that resulted in a transient S1P signal in response to muscle injury. S1P activated quiescent SCs via a sphingosine-1-phosphate receptor 2 (S1P2)/signal transducer and activator of transcription 3 (STAT3)-dependent pathway, thereby facilitating skeletal muscle regeneration. Mdx mice, which serve as a model for muscular dystrophy (MD), exhibited skeletal muscle SPL upregulation and S1P deficiency. Pharmacological SPL inhibition raised skeletal muscle S1P levels, enhanced SC recruitment and improved mdx skeletal muscle regeneration. These findings reveal how S1P can activate SCs and indicate that SPL suppression may provide a therapeutic strategy for myopathies. This article is part of a Special Issue entitled Advances in Lysophospholipid Research. PMID:22750505

  1. Catalytic Cage Formation via Controlled Dimerization of Norbornadienes: An Entry to Functionalized HCTDs (Heptacyclo[6.6.0.0(2,6).0(3,13).0(4,11).0(5,9).0(10,14)]tetradecanes).

    PubMed

    Lim, Hee Nam; Dong, Guangbin

    2016-03-01

    A general and practical catalytic method has been developed for the rapid synthesis of HCTD (heptacyclo[6.6.0.0(2,6).0(3,13).0(4,11).0(5,9).0(10,14)]tetradecanes) and various new 7,12-disubstituted HCTDs from norbornadienes. Compared to the known approaches, this new protocol avoids stoichiometric metals, utilizes commercially available reagents as catalysts, and affords higher yields and significantly improved selectivity. In addition, quadracyclane was discovered for the first time to undergo a similar endo,cis,endo cycloaddition to give HCTD in a good yield. Derivatization of HCTDs led to efficient preparation of a range of novel homo- and heterobifunctional scaffolds that hold potentials for biological and material applications. PMID:26862783

  2. The Vicência meteorite fall: A new unshocked (S1) weakly metamorphosed (3.2) LL chondrite

    NASA Astrophysics Data System (ADS)

    Keil, Klaus; Zucolotto, Maria E.; Krot, Alexander N.; Doyle, Patricia M.; Telus, Myriam; Krot, Tatiana V.; Greenwood, Richard C.; Franchi, Ian A.; Wasson, John T.; Welten, Kees C.; Caffee, Marc W.; Sears, Derek W. G.; Riebe, My; Wieler, Rainer; Santos, Edivaldo; Scorzelli, Rosa B.; Gattacceca, Jerome; Lagroix, France; Laubenstein, Matthias; Mendes, Julio C.; Schmitt-Kopplin, Philippe; Harir, Mourad; Moutinho, Andre L. R.

    2015-06-01

    The Vicência meteorite, a stone of 1.547 kg, fell on September 21, 2013, at the village Borracha, near the city of Vicência, Pernambuco, Brazil. It was recovered immediately after the fall, and our consortium study showed it to be an unshocked (S1) LL3.2 ordinary chondrite. The LL group classification is based on the bulk density (3.13 g cm-3); the chondrule mean apparent diameter (0.9 mm); the bulk oxygen isotopic composition (δ17O = 3.768 ± 0.042‰, δ18O = 5.359 ± 0.042‰, Δ17O = 0.981 ± 0.020‰); the content of metallic Fe,Ni (1.8 vol%); the Co content of kamacite (1.73 wt%); the bulk contents of the siderophile elements Ir and Co versus Au; and the ratios of metallic Fe0/total iron (0.105) versus total Fe/Mg (1.164), and of Ni/Mg (0.057) versus total Fe/Mg. The petrologic type 3.2 classification is indicated by the beautifully developed chondritic texture, the standard deviation (~0.09) versus mean Cr2O3 content (~0.14 wt%) of ferroan olivine, the TL sensitivity and the peak temperature and peak width at half maximum, the cathodoluminescence properties of chondrules, the content of trapped 132Xetr (0.317 × 10-8cm3STP g-1), and the Raman spectra for organic material in the matrix. The cosmic ray exposure age is ~72 Ma, which is at the upper end of the age distribution of LL group chondrites. The meteorite is unusual in that it contains relatively large, up to nearly 100 μm in size, secondary fayalite grains, defined as olivine with Fa>75, large enough to allow in situ measurement of oxygen and Mn-Cr isotope systematics with SIMS. Its oxygen isotopes plot along a mass-dependent fractionation line with a slope of ~0.5 and Δ17O of 4.0 ± 0.3‰, and are similar to those of secondary fayalite and magnetite in the unequilibrated chondrites EET 90161, MET 96503, and Ngawi. These data suggest that secondary fayalite in Vicência was in equilibrium with a fluid with a Δ17O of ~4‰, consistent with the composition of the fluid in equilibrium with

  3. Synthesis of new ligands for targeting the S1P1 receptor.

    PubMed

    Schilson, Stefanie S; Keul, Petra; Shaikh, Rizwan S; Schäfers, Michael; Levkau, Bodo; Haufe, Günter

    2015-03-01

    Sphingosine-1-phosphate (S1P) influences various fundamental biological processes by interacting with a family of five G protein-coupled receptors (S1P1-5). FTY720, a sphingosine analogue, which was approved for treatment of relapsing forms of multiple sclerosis, is phosphorylated in vivo and acts as an agonist of four of the five S1P receptor subtypes. Starting from these lead structures we developed new agonists for the S1P1 receptor. The biological activity was tested in vivo and promising ligands were fluorinated at different positions to identify candidates for positron emission tomography (PET) imaging after [(18)F]-labelling. The radioligands shall enable the imaging of S1P1 receptor expression in vivo and thus may serve as novel imaging markers of S1P-related diseases. PMID:25656338

  4. S1PR1-mediated IFNAR1 degradation modulates plasmacytoid dendritic cell interferon-α autoamplification

    PubMed Central

    Teijaro, John R.; Studer, Sean; Leaf, Nora; Kiosses, William B.; Nguyen, Nhan; Matsuki, Kosuke; Negishi, Hideo; Taniguchi, Tadatsugu; Oldstone, Michael B. A.; Rosen, Hugh

    2016-01-01

    Blunting immunopathology without abolishing host defense is the foundation for safe and effective modulation of infectious and autoimmune diseases. Sphingosine 1-phosphate receptor 1 (S1PR1) agonists are effective in treating infectious and multiple autoimmune pathologies; however, mechanisms underlying their clinical efficacy are yet to be fully elucidated. Here, we uncover an unexpected mechanism of convergence between S1PR1 and interferon alpha receptor 1 (IFNAR1) signaling pathways. Activation of S1PR1 signaling by pharmacological tools or endogenous ligand sphingosine-1 phosphate (S1P) inhibits type 1 IFN responses that exacerbate numerous pathogenic conditions. Mechanistically, S1PR1 selectively suppresses the type I IFN autoamplification loop in plasmacytoid dendritic cells (pDCs), a specialized DC subset, for robust type I IFN release. S1PR1 agonist suppression is pertussis toxin-resistant, but inhibited by an S1PR1 C-terminal–derived transactivating transcriptional activator (Tat)-fusion peptide that blocks receptor internalization. S1PR1 agonist treatment accelerates turnover of IFNAR1, suppresses signal transducer and activator of transcription 1 (STAT1) phosphorylation, and down-modulates total STAT1 levels, thereby inactivating the autoamplification loop. Inhibition of S1P-S1PR1 signaling in vivo using the selective antagonist Ex26 significantly elevates IFN-α production in response to CpG-A. Thus, multiple lines of evidence demonstrate that S1PR1 signaling sets the sensitivity of pDC amplification of IFN responses, thereby blunting pathogenic immune responses. These data illustrate a lipid G-protein coupled receptor (GPCR)-IFNAR1 regulatory loop that balances effective and detrimental immune responses and elevated endogenous S1PR1 signaling. This mechanism will likely be advantageous in individuals subject to a range of inflammatory conditions. PMID:26787880

  5. STS-112 S1 Truss is transported to the payload canister

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- An overhead crane lifts the S1 Integrated Truss Structure from its workstand. The S1 will be placed in the payload canister for transport it to Atlantis. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during mission STS-112. Atlantis is scheduled to launch no earlier than Oct. 2.

  6. Intersystem crossing rates of S1 state keto-amino cytosine at low excess energy.

    PubMed

    Lobsiger, Simon; Etinski, Mihajlo; Blaser, Susan; Frey, Hans-Martin; Marian, Christel; Leutwyler, Samuel

    2015-12-21

    The amino-keto tautomer of supersonic jet-cooled cytosine undergoes intersystem crossing (ISC) from the v = 0 and low-lying vibronic levels of its S1((1)ππ(∗)) state. We investigate these ISC rates experimentally and theoretically as a function of S1 state vibrational excess energy Eexc. The S1 vibronic levels are pumped with a ∼5 ns UV laser, the S1 and triplet state ion signals are separated by prompt or delayed ionization with a second UV laser pulse. After correcting the raw ISC yields for the relative S1 and T1 ionization cross sections, we obtain energy dependent ISC quantum yields QISC (corr)=1%-5%. These are combined with previously measured vibronic state-specific decay rates, giving ISC rates kISC = 0.4-1.5 ⋅ 10(9) s(-1), the corresponding S1⇝S0 internal conversion (IC) rates are 30-100 times larger. Theoretical ISC rates are computed using SCS-CC2 methods, which predict rapid ISC from the S1; v = 0 state with kISC = 3 ⋅ 10(9) s(-1) to the T1((3)ππ(∗)) triplet state. The surprisingly high rate of this El Sayed-forbidden transition is caused by a substantial admixture of (1)nOπ(∗) character into the S1((1)ππ(∗)) wave function at its non-planar minimum geometry. The combination of experiment and theory implies that (1) below Eexc = 550 cm(-1) in the S1 state, S1⇝S0 internal conversion dominates the nonradiative decay with kIC ≥ 2 ⋅ 10(10) s(-1), (2) the calculated S1⇝T1 ((1)ππ(∗)⇝(3)ππ(∗)) ISC rate is in good agreement with experiment, (3) being El-Sayed forbidden, the S1⇝T1 ISC is moderately fast (kISC = 3 ⋅ 10(9) s(-1)), and not ultrafast, as claimed by other calculations, and (4) at Eexc ∼ 550 cm(-1) the IC rate increases by ∼50 times, probably by accessing the lowest conical intersection (the C5-twist CI) and thereby effectively switching off the ISC decay channels. PMID:26696056

  7. Intersystem crossing rates of S1 state keto-amino cytosine at low excess energy

    NASA Astrophysics Data System (ADS)

    Lobsiger, Simon; Etinski, Mihajlo; Blaser, Susan; Frey, Hans-Martin; Marian, Christel; Leutwyler, Samuel

    2015-12-01

    The amino-keto tautomer of supersonic jet-cooled cytosine undergoes intersystem crossing (ISC) from the v = 0 and low-lying vibronic levels of its S1(1ππ∗) state. We investigate these ISC rates experimentally and theoretically as a function of S1 state vibrational excess energy Eexc. The S1 vibronic levels are pumped with a ˜5 ns UV laser, the S1 and triplet state ion signals are separated by prompt or delayed ionization with a second UV laser pulse. After correcting the raw ISC yields for the relative S1 and T1 ionization cross sections, we obtain energy dependent ISC quantum yields QISC corr = 1 % -5%. These are combined with previously measured vibronic state-specific decay rates, giving ISC rates kISC = 0.4-1.5 ṡ 109 s-1, the corresponding S1⇝S0 internal conversion (IC) rates are 30-100 times larger. Theoretical ISC rates are computed using SCS-CC2 methods, which predict rapid ISC from the S1; v = 0 state with kISC = 3 ṡ 109 s-1 to the T1(3ππ∗) triplet state. The surprisingly high rate of this El Sayed-forbidden transition is caused by a substantial admixture of 1nOπ∗ character into the S1(1ππ∗) wave function at its non-planar minimum geometry. The combination of experiment and theory implies that (1) below Eexc = 550 cm-1 in the S1 state, S1⇝S0 internal conversion dominates the nonradiative decay with kIC ≥ 2 ṡ 1010 s-1, (2) the calculated S1⇝T1 (1ππ∗⇝3ππ∗) ISC rate is in good agreement with experiment, (3) being El-Sayed forbidden, the S1⇝T1 ISC is moderately fast (kISC = 3 ṡ 109 s-1), and not ultrafast, as claimed by other calculations, and (4) at Eexc ˜ 550 cm-1 the IC rate increases by ˜50 times, probably by accessing the lowest conical intersection (the C5-twist CI) and thereby effectively switching off the ISC decay channels.

  8. BaV3O8: A possible Majumdar-Ghosh system with S = (1)/(2)

    NASA Astrophysics Data System (ADS)

    Chakrabarty, T.; Mahajan, A. V.; Gippius, A. A.; Tkachev, A. V.; Büttgen, N.; Kraetschmer, W.

    2013-07-01

    BaV3O8 contains magnetic V4+(S=1/2) ions and also nonmagnetic V5+(S=0) ions. The V4+ ions are arranged in a coupled Majumdar-Ghosh chainlike network. A Curie-Weiss fit of our magnetic susceptibility χ(T) data in the temperature region of 80-300 K yields a Curie constant C=0.39 cm3K/mole V4+ and an antiferromagnetic Weiss temperature θ=-26K. The χ(T) curve shows a broad maximum at T≃25 K indicative of short-range order (SRO) and an anomaly corresponding to long-range order (LRO) at TN˜6 K. The value of the “frustration parameter” (f=|θ/TN|˜5) suggests that the system is moderately frustrated. Above the LRO temperature, the experimental magnetic susceptibility data match well with the coupled Majumdar-Ghosh (or Jnn-Jnnn Heisenberg) chain model with the ratio of the nnn (next-nearest neighbor) to nn (nearest neighbor) magnetic coupling α=2 and Jnnn/kB=40 K. In a mean-field approach when considering the interchain interactions, we obtain the total interchain coupling to be about 16 K. The LRO anomaly at TN is also observed in the specific heat CP(T) data and is not sensitive to an applied magnetic field up to 90 kOe. A 51V NMR signal corresponding to the nonmagnetic vanadium was observed. Anomalies at 6 K were observed in the variation with temperature of the 51V NMR linewidth and the spin-lattice relaxation rate 1/T1 indicating that they are sensitive to the LRO onset and fluctuations at the magnetic V sites. The existence of two components (one short and another long) is observed in the spin-spin relaxation rate 1/T2 data in the vicinity of TN. The shorter component seems to be intimately connected with the magnetically ordered state. We suggest that both magnetically ordered and nonlong-range-ordered (non-LRO) regions coexist in this compound below the long-range-ordering temperature.

  9. Blocking peptides against HBV: PreS1 protein selected from a phage display library

    SciTech Connect

    Wang, Wei; Liu, Yang; Zu, Xiangyang; Jin, Rui; Xiao, Gengfu

    2011-09-09

    Highlights: {yields} Successfully selected specific PreS1-interacting peptides by using phage displayed library. {yields} Alignment of the positive phage clones revealed a consensus PreS1 binding motif. {yields} A highly enriched peptide named P7 had a strong binding ability for PreS1. {yields} P7 could block PreS1 attachment. -- Abstract: The PreS1 protein is present on the outermost part of the hepatitis B virus (HBV) surface and has been shown to have a pivotal function in viral infectivity and assembly. The development of reagents with high affinity and specificity for PreS1 is of great significance for early diagnosis and treatment of HBV infection. A phage display library of dodecapeptide was screened for interactions with purified PreS1 protein. Alignment of the positive phage clones revealed a putative consensus PreS1 binding motif of HX{sub n}HX{sub m}HP/R. Moreover, a peptide named P7 (KHMHWHPPALNT) was highly enriched and occurred with a surprisingly high frequency of 72%. A thermodynamic study revealed that P7 has a higher binding affinity to PreS1 than the other peptides. Furthermore, P7 was able to abrogate the binding of HBV virions to the PreS1 antibody, suggesting that P7 covers key functional sites on the native PreS1 protein. This newly isolated peptide may, therefore, be a new therapeutic candidate for the treatment of HBV. The consensus motif could be modified to deliver imaging, diagnostic, and therapeutic agents to tissues affected by HBV.

  10. Effect of ADP on binding of skeletal S1 to F-actin.

    PubMed

    Andreev, O A; Ushakov, D S; Borejdo, J

    1998-12-22

    The proximity of skeletal myosin subfragment-1 (S1) to actin, and its orientation with respect to thin filaments of single muscle fibers, were compared in the presence and in the absence of ADP. The proximity was assessed by the efficiency of carbodiimide-induced cross-linking and the orientation by polarization of fluorescence of probes attached to the essential light chains. ADP made no difference in proximity or orientation when the molar ratio of S1 to actin was low or high. However, at the intermediate ratios, ADP made a significant difference. Strong dissociating agents, AMP-PNP and PPi, made significant differences at all ratios. To explain this behavior, it is unnecessary to invoke the ADP-induced "swinging" of the tail of S1. Rather, it is simply explained by the "two-state" model which we proposed earlier, in which S1 binds to one or to two actin protomers, depending on the saturation of the filaments with S1s. The dissociation induced by the ADP shifts the equilibrium between the two bound states. At high and low degrees of saturation, ADP is unable to significantly decrease the amount of S1 bound to F-actin. However, at intermediate saturation levels, ADP causes significantly more S1s to bind to two actins. These results suggest that the ADP-induced changes seen at the intermediate molar ratios are due to the dissociation-induced reorientation of S1. PMID:9922150

  11. Calcium alone does not fully activate the thin filament for S1 binding to rigor myofibrils.

    PubMed Central

    Swartz, D R; Moss, R L; Greaser, M L

    1996-01-01

    Skeletal muscle contraction is regulated by calcium via troponin and tropomyosin and appears to involve cooperative activation of cross-bridge binding to actin. We studied the regulation of fluorescent myosin subfragment 1 (fS1) binding to rigor myofibrils over a wide range of fS1 and calcium levels using highly sensitive imaging techniques. At low calcium and low fS1, the fluorescence was restricted to the actin-myosin overlap region. At high calcium and very low fS1, the fluorescence was still predominantly in the overlap region. The ratio of nonoverlap to overlap fluorescence intensity showed that increases in the fS1 level resulted in a shift in maximum fluorescence from the overlap to the nonoverlap region at both low and high calcium; this transition occurred at lower fS1 levels in myofibrils with high calcium. At a fixed fS1 level, increases in calcium also resulted in a shift in maximum fluorescence from the overlap region to the nonoverlap region. These results suggest that calcium alone does not fully activate the thin filament for rigor S1 binding and that, even at high calcium, the thin filament is not activated along its entire length. Images FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 7 FIGURE 9 FIGURE 11 PMID:8889164

  12. Enhanced Raman scattering from cesium suboxides on silver particles and the structure of S-1 photocathodes

    NASA Technical Reports Server (NTRS)

    Bates, C. W., Jr.

    1984-01-01

    An explanation is given for the results of recent enhanced Raman scattering studies of photomultiplier tubes with S-1 photocathode surfaces which indicated the presence of Cs11O3 but not Cs2O. The reason for the discrepancy between the currently accepted model of the S-1 and this recent result is discussed.

  13. VIEW OF THE FROM SIDE OF WHARF S1 FROM WEST ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF THE FROM SIDE OF WHARF S1 FROM WEST END OF QUARRY LOCK, FACING NORTHWEST - U.S. Naval Base, Pearl Harbor, Naval Submarine Base, Berthing Wharf S1, South Waterfront Road along north side of Quarry Loch, Pearl City, Honolulu County, HI

  14. STS-112 S1 Truss is transported to the payload canister

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- An overhead crane moves the S1 Integrated Truss Structure toward the payload canister, which will transport it to Atlantis. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during mission STS-112. Atlantis is scheduled to launch no earlier than Oct. 2.

  15. STS-112 S1 Truss is transported to the payload canister

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- The S1 Integrated Truss Structure is lowered into the payload canister for transport to Atlantis. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during mission STS-112. Atlantis is scheduled to launch no earlier than Oct. 2.

  16. STS-112 S1 Truss is transported to the payload canister

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- An overhead crane moves the S1 Integrated Truss Structure toward the payload canister below, which will transport it to Atlantis. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during mission STS-112. Atlantis is scheduled to launch no earlier than Oct. 2.

  17. Estimates of epistatic and pleiotropic effects of casein alpha s1 (CSN1S1) and thyroglobulin (TG) genetic markers on beef heifer performance traits enhanced by selection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. A stable composite population (MARC II) was subjected to marker assisted selection for two years to equalize CSN1S1 and TG genetic marker frequencies to evaluate the epista...

  18. The influence of fetal sex in screening for trisomy 21 by fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation.

    PubMed

    Spencer, K; Ong, C Y; Liao, A W; Papademetriou, D; Nicolaides, K H

    2000-08-01

    In a study of 2923 normal pregnancies and 203 pregnancies affected by trisomy 21 we have shown a significant difference in the median MoM of the markers: fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A in the presence of a female fetus compared with a male fetus. For maternal serum free beta-hCG levels are higher by 15% if the fetus is chromosomally normal and by 11% if the fetus has trisomy 21. For maternal serum PAPP-A the levels in chromosomally normal fetuses are 10% higher in the presence of a female fetus and 13% higher if the fetus has trisomy 21. In contrast, fetal nuchal translucency is 3-4% lower in both chromosomally normal and trisomy 21 female fetuses. The consequence of such changes when screening for trisomy 21 will be a reduction in the detection rate in female fetuses by a factor of 1-2%. Correction of risk algorithms for fetal sex, however, is probably not feasible, since ultrasound detection of fetal sex is only 70-90% accurate in the 10-14 week period. PMID:10951481

  19. Ribosomal protein S1 induces a conformational change of tmRNA; more than one protein S1 per molecule of tmRNA.

    PubMed

    Bordeau, Valérie; Felden, Brice

    2002-08-01

    tmRNA (10Sa RNA, ssrA) acts to rescue stalled bacterial ribosomes while encoding a peptide tag added trans-translationally to the nascent peptide, targeting it for proteolysis. Ribosomal protein S1 is required for tmRNA binding to isolated and poly U-programmed ribosomes. Mobility assays on native gels indicate that the binding curves of both recombinant and purified proteins S1 from E. coli is biphasic with apparent binding constants of approximately 90 and approximately 300 nM, respectively, suggesting that more than one protein interacts with tmRNA. Structural probing of native tmRNA in the presence and absence of the purified protein suggest that when S1 binds, tmRNA undergoes a significant conformational change. In the presence of the protein, nucleotides from tmRNA with enhanced (H2, H3, PK1, PK2, PK4, in and around the first triplet to be translated), or decreased (H5 and PK2), reactivity towards a probe specific for RNA single-strands are scattered throughout the molecule, with the exception of the tRNA-like domain that may be dispensable for the interaction. Converging experimental evidence suggests that ribosomal protein S1 binds to pseudoknot PK2. Previous structural studies of tmRNA in solution have revealed several discrepancies between the probing data and the phylogeny, and most of these are reconciled when analyzing tmRNA structure in complex with the protein(s). Ribosomal protein(s) S1 is proposed to set tmRNA in the mRNA mode, relieving strains that may develop when translating a looped mRNA. PMID:12457560

  20. Molecular insights into replication initiation by Qβ replicase using ribosomal protein S1

    PubMed Central

    Takeshita, Daijiro; Yamashita, Seisuke; Tomita, Kozo

    2014-01-01

    Ribosomal protein S1, consisting of six contiguous OB-folds, is the largest ribosomal protein and is essential for translation initiation in Escherichia coli. S1 is also one of the three essential host-derived subunits of Qβ replicase, together with EF-Tu and EF-Ts, for Qβ RNA replication in E. coli. We analyzed the crystal structure of Qβ replicase, consisting of the virus-encoded RNA-dependent RNA polymerase (β-subunit), EF-Tu, EF-Ts and the N-terminal half of S1, which is capable of initiating Qβ RNA replication. Structural and biochemical studies revealed that the two N-terminal OB-folds of S1 anchor S1 onto the β-subunit, and the third OB-fold is mobile and protrudes beyond the surface of the β-subunit. The third OB-fold mainly interacts with a specific RNA fragment derived from the internal region of Qβ RNA, and its RNA-binding ability is required for replication initiation of Qβ RNA. Thus, the third mobile OB-fold of S1, which is spatially anchored near the surface of the β-subunit, primarily recruits the Qβ RNA toward the β-subunit, leading to the specific and efficient replication initiation of Qβ RNA, and S1 functions as a replication initiation factor, beyond its established function in protein synthesis. PMID:25122749

  1. One-stage surgery through posterior approach-for L5-S1 spondyloptosis

    PubMed Central

    Suslu, Hikmet Turan; Celikoglu, Erhan; Borekcı, Ali; Hıcdonmez, Tufan; Suslu, Hüsnü

    2011-01-01

    Grade 5 spondylolisthesis or spondyloptosis is a rare condition. Generally, the surgical management of spondyloptosis includes multi-staged procedures instead of one-staged procedures. One-stage treatment for spondyloptosis is very rare. A 15-year-old girl with L5-S1 spondyloptosis was admitted with severe low back pain. There was no history of trauma. The patient underwent L5 laminectomy, L5-S1 discectomy, resection of sacral dome, reduction, L3-L4-L5-S1 pedicular screw fixation, and interbody-posterolateral fusion through the posterior approach. The reduction was maintained with bilateral L5-S1 discectomy, resection of the sacral dome, and transpedicular instrumentation from L3 to S1. In this particular case, one-staged approach was adequate for the treatment of L5-S1 spondyloptosis. One-staged surgery using the posterior approach may be adequate for the treatment of L5-S1 spondyloptosis while avoiding the risks inherent in anterior approaches. PMID:23125496

  2. [Combination therapy with S-1 and CDDP for head and neck cancer].

    PubMed

    Fujii, Masato

    2006-06-01

    The combination with cisplatin (CDDP) and 5-FU is considered the first choice chemotherapy for squamous cell carcinoma of the head and neck (HNSCC). S-1, a modulation of tegafur developed in Japan, is an active agent for HNSCC. Some clinical phase I/II studies about the combination with CDDP and S-1 have been reported. The combination showed a good response rate of 67.6% for advanced and recurrent HNSCC in our clinical phase I/II study. The regimens of S-1 combined with carboplatin or nedaplatin have also been reported. Regimens containing S-1 appear to have been effective for HNSCC. Multi-institutional phase II studies with a large sample size are needed in the future. The compliance for patients is better than a 5-FU injection because S-1 is orally administrated. The adverse effect, especially for bone mallow toxicity, is equal or upgraded compared with a 5-FU injection. The efficacy and adverse effects of CDDP plus S-1 should be studied in carefully designed phase II/III trials. S-1 will be one of the key drugs for HNSCC in the future. PMID:16897992

  3. The vascular S1P gradient—Cellular sources and biological significance

    PubMed Central

    Hla, Timothy; Venkataraman, Krishnan; Michaud, Jason

    2009-01-01

    Sphingosine 1-phosphate (S1P), a product of sphingomyelin metabolism, is enriched in the circulatory system whereas it is estimated to be much lower in interstitial fluids of tissues. This concentration gradient, termed the vascular S1P gradient appears to form as a result of substrate availability and the action of metabolic enzymes. S1P levels in blood and lymph are estimated to be in the μM range. In the immune system, the S1P gradient is needed as a spatial cue for lymphocyte and hematopoietic cell trafficking. During inflammatory reactions in which enhanced vascular permeability occurs, a burst of S1P becomes available to its receptors in the extravascular compartment, which likely contributes to the tissue reactions. Thus, the presence of the vascular S1P gradient is thought to contribute to physiological and pathological conditions. From an evolutionary perspective, S1P receptors may have co-evolved with the advent of a closed vascular system and the trafficking paradigms for hematopoietic cells to navigate in and out of the vascular system. PMID:18674637

  4. Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants within S1PR2.

    PubMed

    Santos-Cortez, Regie Lyn P; Faridi, Rabia; Rehman, Atteeq U; Lee, Kwanghyuk; Ansar, Muhammad; Wang, Xin; Morell, Robert J; Isaacson, Rivka; Belyantseva, Inna A; Dai, Hang; Acharya, Anushree; Qaiser, Tanveer A; Muhammad, Dost; Ali, Rana Amjad; Shams, Sulaiman; Hassan, Muhammad Jawad; Shahzad, Shaheen; Raza, Syed Irfan; Bashir, Zil-E-Huma; Smith, Joshua D; Nickerson, Deborah A; Bamshad, Michael J; Riazuddin, Sheikh; Ahmad, Wasim; Friedman, Thomas B; Leal, Suzanne M

    2016-02-01

    The sphingosine-1-phosphate receptors (S1PRs) are a well-studied class of transmembrane G protein-coupled sphingolipid receptors that mediate multiple cellular processes. However, S1PRs have not been previously reported to be involved in the genetic etiology of human traits. S1PR2 lies within the autosomal-recessive nonsyndromic hearing impairment (ARNSHI) locus DFNB68 on 19p13.2. From exome sequence data we identified two pathogenic S1PR2 variants, c.323G>C (p.Arg108Pro) and c.419A>G (p.Tyr140Cys). Each of these variants co-segregates with congenital profound hearing impairment in consanguineous Pakistani families with maximum LOD scores of 6.4 for family DEM4154 and 3.3 for family PKDF1400. Neither S1PR2 missense variant was reported among ∼120,000 chromosomes in the Exome Aggregation Consortium database, in 76 unrelated Pakistani exomes, or in 720 Pakistani control chromosomes. Both DNA variants affect highly conserved residues of S1PR2 and are predicted to be damaging by multiple bioinformatics tools. Molecular modeling predicts that these variants affect binding of sphingosine-1-phosphate (p.Arg108Pro) and G protein docking (p.Tyr140Cys). In the previously reported S1pr2(-/-) mice, stria vascularis abnormalities, organ of Corti degeneration, and profound hearing loss were observed. Additionally, hair cell defects were seen in both knockout mice and morphant zebrafish. Family PKDF1400 presents with ARNSHI, which is consistent with the lack of gross malformations in S1pr2(-/-) mice, whereas family DEM4154 has lower limb malformations in addition to hearing loss. Our findings suggest the possibility of developing therapies against hair cell damage (e.g., from ototoxic drugs) through targeted stimulation of S1PR2. PMID:26805784

  5. Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants within S1PR2

    PubMed Central

    Santos-Cortez, Regie Lyn P.; Faridi, Rabia; Rehman, Atteeq U.; Lee, Kwanghyuk; Ansar, Muhammad; Wang, Xin; Morell, Robert J.; Isaacson, Rivka; Belyantseva, Inna A.; Dai, Hang; Acharya, Anushree; Qaiser, Tanveer A.; Muhammad, Dost; Ali, Rana Amjad; Shams, Sulaiman; Hassan, Muhammad Jawad; Shahzad, Shaheen; Raza, Syed Irfan; Bashir, Zil-e-Huma; Smith, Joshua D.; Nickerson, Deborah A.; Bamshad, Michael J.; Riazuddin, Sheikh; Ahmad, Wasim; Friedman, Thomas B.; Leal, Suzanne M.

    2016-01-01

    The sphingosine-1-phosphate receptors (S1PRs) are a well-studied class of transmembrane G protein-coupled sphingolipid receptors that mediate multiple cellular processes. However, S1PRs have not been previously reported to be involved in the genetic etiology of human traits. S1PR2 lies within the autosomal-recessive nonsyndromic hearing impairment (ARNSHI) locus DFNB68 on 19p13.2. From exome sequence data we identified two pathogenic S1PR2 variants, c.323G>C (p.Arg108Pro) and c.419A>G (p.Tyr140Cys). Each of these variants co-segregates with congenital profound hearing impairment in consanguineous Pakistani families with maximum LOD scores of 6.4 for family DEM4154 and 3.3 for family PKDF1400. Neither S1PR2 missense variant was reported among ∼120,000 chromosomes in the Exome Aggregation Consortium database, in 76 unrelated Pakistani exomes, or in 720 Pakistani control chromosomes. Both DNA variants affect highly conserved residues of S1PR2 and are predicted to be damaging by multiple bioinformatics tools. Molecular modeling predicts that these variants affect binding of sphingosine-1-phosphate (p.Arg108Pro) and G protein docking (p.Tyr140Cys). In the previously reported S1pr2−/− mice, stria vascularis abnormalities, organ of Corti degeneration, and profound hearing loss were observed. Additionally, hair cell defects were seen in both knockout mice and morphant zebrafish. Family PKDF1400 presents with ARNSHI, which is consistent with the lack of gross malformations in S1pr2−/− mice, whereas family DEM4154 has lower limb malformations in addition to hearing loss. Our findings suggest the possibility of developing therapies against hair cell damage (e.g., from ototoxic drugs) through targeted stimulation of S1PR2. PMID:26805784

  6. Decorin in human oral cancer: A promising predictive biomarker of S-1 neoadjuvant chemosensitivity

    SciTech Connect

    Kasamatsu, Atsushi; Uzawa, Katsuhiro; Minakawa, Yasuyuki; Ishige, Shunsaku; Kasama, Hiroki; Endo-Sakamoto, Yosuke; Ogawara, Katsunori; Shiiba, Masashi; Takiguchi, Yuichi; Tanzawa, Hideki

    2015-01-30

    Highlights: • DCN is significantly up-regulated in chemoresistant cancer cell lines. • DCN is a key regulator for chemoresistant mechanisms in vitro and in vivo. • DCN predicts the clinical responses to S-1 NAC for patients with oral cancer. - Abstract: We reported previously that decorin (DCN) is significantly up-regulated in chemoresistant cancer cell lines. DCN is a small leucine-rich proteoglycan that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that DCN affects the biology of several types of cancer by directly/indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis, however, the molecular mechanisms of DCN in chemoresistance and its clinical relevance are still unknown. Here we assumed that DCN silencing cells increase chemosusceptibility to S-1, consisted of tegafur, prodrug of 5-fluorouracil. We first established DCN knockdown transfectants derived from oral cancer cells for following experiments including chemosusceptibility assay to S-1. In addition to the in vitro data, DCN knockdown zenografting tumors in nude mice demonstrate decreasing cell proliferation and increasing apoptosis with dephosphorylation of AKT after S-1 chemotherapy. We also investigated whether DCN expression predicts the clinical responses of neoadjuvant chemotherapy (NAC) using S-1 (S-1 NAC) for oral cancer patients. Immunohistochemistry data in the preoperative biopsy samples was analyzed to determine the cut-off point for status of DCN expression by receiver operating curve analysis. Interestingly, low DCN expression was observed in five (83%) of six cases with complete responses to S-1 NAC, and in one (10%) case of 10 cases with stable/progressive disease, indicating that S-1 chemosensitivity is dramatically effective in oral cancer patients with low DCN expression compared with high DCN expression. Our findings suggest that DCN is a key regulator for chemoresistant mechanisms, and

  7. S = 1 Excitations in Heat Capacity of the Haldane Compound TMNIN Doped with a Nonmagnetic Impurity

    NASA Astrophysics Data System (ADS)

    Kawae, Tatsuya; Ito, Masakazu; Mito, Masaki; Takeda, Kazuyoshi

    1999-03-01

    We have studied the field dependence of the heat capacity of a typicalHaldane antiferromagnet (CH3)4NNi(NO)3 (TMNIN) doped with thenonmagnetic impurity Zn2+, as well as of a pure TMNIN. The overallfeatures of the magnetic heat capacity, including the characteristic broadmaximum, are almost reproduced by the theoretical curve with J/k B =-12 K for both systems in zero field. The field dependence in the impuresystems is described well by assuming the Schottky heat capacity with S =1, not S = 1/2 expected from the VBS model. A possible reason why the S= 1 model is suitable is discussed.

  8. Exercise Capacity and Response to Training Quantitative Trait Loci in a NZW X 129S1 Intercross and Combined Cross Analysis of Inbred Mouse Strains

    PubMed Central

    Massett, Michael P.; Avila, Joshua J.; Kim, Seung Kyum

    2015-01-01

    Genetic factors determining exercise capacity and the magnitude of the response to exercise training are poorly understood. The aim of this study was to identify quantitative trait loci (QTL) associated with exercise training in mice. Based on marked differences in training responses in inbred NZW (-0.65 ± 1.73 min) and 129S1 (6.18 ± 3.81 min) mice, a reciprocal intercross breeding scheme was used to generate 285 F2 mice. All F2 mice completed an exercise performance test before and after a 4-week treadmill running program, resulting in an increase in exercise capacity of 1.54 ± 3.69 min (range = -10 to +12 min). Genome-wide linkage scans were performed for pre-training, post-training, and change in run time. For pre-training exercise time, suggestive QTL were identified on Chromosomes 5 (57.4 cM, 2.5 LOD) and 6 (47.8 cM, 2.9 LOD). A significant QTL for post-training exercise capacity was identified on Chromosome 5 (43.4 cM, 4.1 LOD) and a suggestive QTL on Chromosomes 1 (55.7 cM, 2.3 LOD) and 8 (66.1 cM, 2.2 LOD). A suggestive QTL for the change in run time was identified on Chromosome 6 (37.8 cM, 2.7 LOD). To identify shared QTL, this data set was combined with data from a previous F2 cross between B6 and FVB strains. In the combined cross analysis, significant novel QTL for pre-training exercise time and change in exercise time were identified on Chromosome 12 (54.0 cM, 3.6 LOD) and Chromosome 6 (28.0 cM, 3.7 LOD), respectively. Collectively, these data suggest that combined cross analysis can be used to identify novel QTL and narrow the confidence interval of QTL for exercise capacity and responses to training. Furthermore, these data support the use of larger and more diverse mapping populations to identify the genetic basis for exercise capacity and responses to training. PMID:26710100

  9. Expression of S1P metabolizing enzymes and receptors correlate with survival time and regulate cell migration in glioblastoma multiforme

    PubMed Central

    Bien-Möller, Sandra; Lange, Sandra; Holm, Tobias; Böhm, Andreas; Paland, Heiko; Küpper, Johannes; Herzog, Susann; Weitmann, Kerstin; Havemann, Christoph; Vogelgesang, Silke; Marx, Sascha; Hoffmann, Wolfgang; Schroeder, Henry W.S.; Rauch, Bernhard H.

    2016-01-01

    A signaling molecule which is involved in proliferation and migration of malignant cells is the lipid mediator sphingosine-1-phosphate (S1P). There are hints for a potential role of S1P signaling in malignant brain tumors such as glioblastoma multiforme (GBM) which is characterized by a poor prognosis. Therefore, a comprehensive expression analysis of S1P receptors (S1P1-S1P5) and S1P metabolizing enzymes in human GBM (n = 117) compared to healthy brain (n = 10) was performed to evaluate their role for patient's survival. Furthermore, influence of S1P receptor inhibition on proliferation and migration were studied in LN18 GBM cells. Compared to control brain, mRNA levels of S1P1, S1P2, S1P3 and S1P generating sphingosine kinase-1 were elevated in GBM. Kaplan-Meier analyses demonstrated an association between S1P1 and S1P2 with patient's survival times. In vitro, an inhibitory effect of the SphK inhibitor SKI-II on viability of LN18 cells was shown. S1P itself had no effect on viability but stimulated LN18 migration which was blocked by inhibition of S1P1 and S1P2. The participation of S1P1 and S1P2 in LN18 migration was further supported by siRNA-mediated silencing of these receptors. Immunoblots and inhibition experiments suggest an involvement of the PI3-kinase/AKT1 pathway in the chemotactic effect of S1P in LN18 cells. In summary, our data argue for a role of S1P signaling in proliferation and migration of GBM cells. Individual components of the S1P pathway represent prognostic factors for patients with GBM. Perspectively, a selective modulation of S1P receptor subtypes could represent a therapeutic approach for GBM patients and requires further evaluation. PMID:26887055

  10. Plastic flow in shock-loaded silver at strain rates from 104 s-1 to 107 s-1 and temperatures from 296 K to 1233 K

    NASA Astrophysics Data System (ADS)

    Zaretsky, E. B.; Kanel, G. I.

    2011-10-01

    The evolution of elastic-plastic shock waves in 99.9% purity silver samples of 0.127 to 2.0 mm thickness has been studied in a series of VISAR-instrumented planar impact experiments with initial sample temperature varied from 296 to 1233 K. The decay of elastic precursor wave at 933, 1173, and 1233 K temperatures is approximately inversely proportional to the square root of the propagation distance. The latter corresponds to the cubic dependence of initial plastic strain rate, ranged from 104 s-1 to 106 s-1, on the shear stress. At fixed strain rates, the flow stress grows linearly with the temperature but the dependence becomes stronger near the silver melting point, 1234 K. An analysis of the rise times of the plastic shock waves shows that for the same level of shear stress the plastic strain rate at the shock front is significantly higher than that at the top of the elastic precursor wave.

  11. Components-dependent optical nonlinearity in a series of CdSexS1-x and CdSexS1-x/ZnS QDs

    NASA Astrophysics Data System (ADS)

    Zhao, Shunlong; Wu, Feng; Zhang, Siwen; Wang, Qian; Li, Songtao; Cheng, Xiaoman

    2016-08-01

    The different compositions of the ternary alloyed CdSexS1-x and CdSexS1-x/ZnS core/shell quantum dots(CSQDs) have been synthesized by the chemical routes. The nonlinear optical properties of these QDs were investigated using Z-scan technique under the excitation of the 1064 nm picosecond laser pulse. The Z-scan results reveal that the nonlinear refractive indices of these QDs can be tuned by changing the ratio of Se and S components. Nonlinear optical (NLO) properties have been shown to be enhanced in CSQDs as compared to their core semiconductor counterparts. These QDs exhibit the components-tuned nonlinear refraction indices, which lead to a wide application in the photonic field.

  12. PMMA Cementoplasty in Symptomatic Metastatic Lesions of the S1 Vertebral Body

    SciTech Connect

    Dehdashti, Amir R.; Martin, Jean-Baptiste; Jean, Beatrix; Ruefenacht, Daniel A.

    2000-03-15

    We describe a lateral transiliac direct puncture approach to the S1 vertebral body for polymethylmethacrylate (PMMA) cementoplasty of painful metastatic lesions. This approach was performed using a 15-cm-long trocar needle with 3-mm outer diameter, introduced under general anesthesia and fluoroscopic control. A lateral projection was used to center the needle just in front of the spinal canal and subjacent to the superior plate of the S1 vertebral body. Needle progression was controlled using anteroposterior and lateral fluoroscopic projections alternately with a needle course parallel to an axial plane, avoiding conflict with the S1 foramen. After needle tip placement in the center of the S1 vertebral body, diluted PMMA with a setting time of 8 min was delivered. Ipsilateral lesions of the lateral sacral compartment were filled with the same needle by stepwise withdrawal and continuous PMMA injection.

  13. The D{sub s1} and its D*K decays

    SciTech Connect

    Segovia, J.; Entem, D. R.; Fernandez, F.

    2010-08-05

    Recently the Belle Collaboration has measured a new decay channel for the charmed strange meson D{sub s1}(2536){sup +{yields}}D{sup +{pi}-}K{sup +} together with an angular analysis of the D{sub s1}(2536){sup +{yields}}D*{sup +}K{sub S}{sup 0} decay. We study this reaction in a constituent quark model which has been able to reproduce the hadronic phenomenology and the baryon-baryon interaction. The reported branching fraction can be explained through a virtual D*{sup 0} and the properties of the D{sub s1}(2536){sup +} state are nicely reproduced. The influence of other intermediate states in the reaction D{sub s1}(2536){sup +{yields}}D{sup +{pi}-}K{sup +} has been analyzed giving negligible contributions.

  14. Intermediate binding of phycocyanobilin to the lyase, CpeS1, and transfer to apoprotein.

    PubMed

    Tu, Jun-Ming; Kupka, Michaela; Böhm, Stephan; Plöscher, Matthias; Eichacker, Lutz; Zhao, Kai-Hong; Scheer, Hugo

    2008-01-01

    The phycobilin: Cysteine-84-phycobiliprotein lyase, CpeS1, catalyzes phycocyanobilin (PCB) and phycoerythrobilin attachment to nearly all cysteine-84 (consensus sequence) binding sites of phycoerythrin, phycoerythrocyanin, phycocyanin and allophycocyanin (Zhao et al. (2007) Proc Natl Acad Sci 104:14300-14305). We now show that CpeS1 can bind PCB, as assayed by Ni(2+) chelating affinity chromatography. Binding is rapid, and the chromophore is bound in an extended conformation similar to that in phycobiliproteins but only poorly fluorescent. Upon addition of apo-biliproteins, the chromophore is transferred to the latter much slower ( approximately 1 h), indicating that chromophorylated CpeS1 is an intermediate in the enzymatic reaction. In addition, imidazole is bound to PCB, as shown by mass spectroscopy of tryptic digests of the intermediate CpeS1-PCB complex. PMID:17912606

  15. Pathway specific modulation of S1P1 receptor signalling in rat and human astrocytes

    PubMed Central

    Healy, Luke M; Sheridan, Graham K; Pritchard, Adam J; Rutkowska, Aleksandra; Mullershausen, Florian; Dev, Kumlesh K

    2013-01-01

    Background and Purpose The sphingosine 1-phosphate receptor subtype 1 (S1P1R) is modulated by phosphorylated FTY720 (pFTY720), which causes S1P1R internalization preventing lymphocyte migration thus limiting autoimmune response. Studies indicate that internalized S1P1Rs continue to signal, maintaining an inhibition of cAMP, thus raising question whether the effects of pFTY720 are due to transient initial agonism, functional antagonism and/or continued signalling. To further investigate this, the current study first determined if continued S1P1R activation is pathway specific. Experimental Approach Using human and rat astrocyte cultures, the effects of S1P1R activation on cAMP, pERK and Ca2+ signalling was investigated. In addition, to examine the role of S1P1R redistribution on these events, a novel biologic (MNP301) that prevented pFTY720-mediated S1P1R redistribution was engineered. Key Results The data showed that pFTY720 induced long-lasting S1P1R redistribution and continued cAMP signalling in rat astrocytes. In contrast, pFTY720 induced a transient increase of Ca2+ in astrocytes and subsequent antagonism of Ca2+ signalling. Notably, while leaving pFTY720-induced cAMP signalling intact, the novel MNP301 peptide attenuated S1P1R-mediated Ca2+ and pERK signalling in cultured rat astrocytes. Conclusions and Implications These findings suggested that pFTY720 causes continued cAMP signalling that is not dependent on S1P1R redistribution and induces functional antagonism of Ca2+ signalling after transient stimulation. To our knowledge, this is the first report demonstrating that pFTY720 causes continued signalling in one pathway (cAMP) versus functional antagonism of another pathway (Ca2+) and which also suggests that redistributed S1P1Rs may have differing signalling properties from those expressed at the surface. PMID:23587004

  16. 3,7,10,14,15-pentaacetyl-5-butanoyl-13,17-epoxy-8-myrsinene a novel compound isolated from Pycnocycla spinosa extract with potent anti-spasmodic and antidiarrheal properties

    PubMed Central

    Sadraei, H.; Ghanadian, M.; Asghari, G.; Sharifian, R.

    2015-01-01

    Bioassay monitoring of hydroalcoholic extract from the aerial part of Pyconcycla spinosa revealed that it contains components with spasmolytic activity in vitro. In addition, P. spinosa extract at oral dose of 1-5 mg/kg inhibits diarrhoea in animal models. Pharmacological screening of pure compounds isolated from P. spinosa hydroalcoholic extract led to the identification of 3,7,10,14,15-pentaacetyl-5-butanoyl-13,17-epoxy-8-myrsinene (PABEM) which is a new diterpene. In this research, we have investigated antispasmodic and antidiarrheal effects of PABEM for comparison with P. spinosa extract. Aerial parts of P. spinosa were extracted with ethanol. For antispasmodic studies, rat isolated ileum was suspended in Tyrode's solution in an organ bath. The ileum was contracted by acetylcholine (ACh, 0.5 μM), serotonin (5-HT, 5 μM) or electrical field stimulation (EFS). P. spinosa extract in a concentration dependent manner (10-640 μg/ml) inhibited ileum contractions induced by ACh, 5-HT or EFS. The new compound isolated form P. spinosa extract “PABEM” in a similar manner inhibited the contractile response to ACh, 5-HT and EFS. However, the inhibitory effects of PABEM were observed at much lower bath concentrations. The relaxation effect of PABEM was started at 40 ng/ml bath concentration and with 2.5 μg/ml PABEM in the bath, the contractile responses of ileum were completely abolished. Both hydroalcoholic extract of P. spinosa and PABEM reduced intestinal meal transit and castor oil and MgSO4 induced diarrhoea in mice. However, PABEM was about 10 times more potent than its parent extract. This research shows that PABEM is probably the main component responsible for antispasmodic and antidiarrheal actions of P. spinosa extract. PMID:26430457

  17. S1P lyase: a novel therapeutic target for ischemia-reperfusion injury of the heart

    PubMed Central

    Bandhuvula, Padmavathi; Honbo, Norman; Wang, Guan-Ying; Jin, Zhu-Qiu; Fyrst, Henrik; Zhang, Meng; Borowsky, Alexander D.; Dillard, Lisa; Karliner, Joel S.

    2011-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that promotes cardiomyocyte survival and contributes to ischemic preconditioning. S1P lyase (SPL) is a stress-activated enzyme responsible for irreversible S1P catabolism. We hypothesized that SPL contributes to oxidative stress by depleting S1P pools available for cardioprotective signaling. Accordingly, we evaluated SPL inhibition as a strategy for reducing cardiac ischemia-reperfusion (I/R) injury. We measured SPL expression and enzyme activity in murine hearts. Basal SPL activity was low in wild-type cardiac tissue but was activated in response to 50 min of ischemia (n = 5, P < 0.01). Hearts of heterozygous SPL knockout mice exhibited reduced SPL activity, elevated S1P levels, smaller infarct size, and increased functional recovery after I/R compared with littermate controls (n = 5, P < 0.01). The small molecule tetrahydroxybutylimidazole (THI) is a Federal Drug Administration-approved food additive that inhibits SPL. When given overnight at 25 mg/l in drinking water, THI raised S1P levels and reduced SPL activity (n = 5, P < 0.01). THI reduced infarct size and enhanced hemodynamic recovery in response to 50 min of ischemia and to 40 min of reperfusion in ex vivo hearts (n = 7, P < .01). These data correlated with an increase in MAP kinase-interacting serine/threonine kinase 1, eukaryotic translation initiation factor 4E, and ribosomal protein S6 phosphorylation levels after I/R, suggesting that SPL inhibition enhances protein translation. Pretreatment with an S1P1 and S1P3 receptor antagonist partially reversed the effects of THI. These results reveal, for the first time, that SPL is an ischemia-induced enzyme that can be targeted as a novel strategy for preventing cardiac I/R injury. PMID:21335477

  18. Characterization of the L4-L5-S1 motion segment using the stepwise reduction method.

    PubMed

    Jaramillo, Héctor Enrique; Puttlitz, Christian M; McGilvray, Kirk; García, José J

    2016-05-01

    The two aims of this study were to generate data for a more accurate calibration of finite element models including the L5-S1 segment, and to find mechanical differences between the L4-L5 and L5-S1 segments. Then, the range of motion (ROM) and facet forces for the L4-S1 segment were measured using the stepwise reduction method. This consists of sequentially testing and reducing each segment in nine stages by cutting the ligaments, facet capsules, and removing the nucleus. Five L4-S1 human segments (median: 65 years, range: 53-84 years, SD=11.0 years) were loaded under a maximum pure moment of 8Nm. The ROM was measured using stereo-photogrammetry via tracking of three markers and the facet contact forces (CF) were measured using a Tekscan system. The ROM for the L4-L5 segment and all stages showed good agreement with published data. The major differences in ROM between the L4-L5 and L5-S1 segments were found for lateral bending and all stages, for which the L4-L5 ROM was about 1.5-3 times higher than that of the L5-S1 segment, consistent with L5-S1 facet CF about 1.3 to 4 times higher than those measured for the L4-L5 segment. For the other movements and few stages, the L4-L5 ROM was significantly lower that of the L5-S1 segment. ROM and CF provide important baseline data for more accurate calibration of FE models and to understand the role that their structures play in lower lumbar spine mechanics. PMID:27017302

  19. STS-112 S1 truss in Payload Changeout Room at Launch Pad 39-B

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- The payload canister is ready to be opened in the Payload Changeout Room at the pad. Inside is the S1 Integrated Truss Structure, primary payload on mission STS-112 aboard Space Shuttle Atlantis. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during the mission. Atlantis is scheduled to launch no earlier than Oct. 2.

  20. 6S-1 RNA function leads to a delay in sporulation in Bacillus subtilis.

    PubMed

    Cavanagh, Amy T; Wassarman, Karen M

    2013-05-01

    We have discovered that 6S-1 RNA (encoded by bsrA) is important for appropriate timing of sporulation in Bacillus subtilis in that cells lacking 6S-1 RNA sporulate earlier than wild-type cells. The time to generate a mature spore once the decision to sporulate has been made is unaffected by 6S-1 RNA, and, therefore, we propose that it is the timing of onset of sporulation that is altered. Interestingly, the presence of cells lacking 6S-1 RNA in coculture leads to all cell types exhibiting an early-sporulation phenotype. We propose that cells lacking 6S-1 RNA modify their environment in a manner that promotes early sporulation. In support of this model, resuspension of wild-type cells in conditioned medium from ΔbsrA cultures also resulted in early sporulation. Use of Escherichia coli growth as a reporter of the nutritional status of conditioned media suggested that B. subtilis cells lacking 6S-1 RNA reduce the nutrient content of their environment earlier than wild-type cells. Several pathways known to impact the timing of sporulation, such as the skf- and sdp-dependent cannibalism pathways, were eliminated as potential targets of 6S-1 RNA-mediated changes, suggesting that 6S-1 RNA activity defines a novel mechanism for altering the timing of onset of sporulation. In addition, 6S-2 RNA does not influence the timing of sporulation, providing further evidence of the independent influences of these two related RNAs on cell physiology. PMID:23457253

  1. STS-112 S1 Truss is transported to the payload canister

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. - Workers inside the payload canister watch the S1 Integrated Truss Structure as it is lowered toward them. The canister will transport the truss to Atlantis. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during mission STS-112. Atlantis is scheduled to launch no earlier than Oct. 2.

  2. STS-112 S1 Truss is transported to the payload canister

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- An overhead crane moves the S1 Integrated Truss Structure above over other equipment to get to the payload canister for transport to Atlantis. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during mission STS-112. Atlantis is scheduled to launch no earlier than Oct. 2.

  3. Ultrafast S1 to S0 internal conversion dynamics for dimethylnitramine through a conical intersection.

    PubMed

    Guo, Yuanqing; Bhattacharya, Atanu; Bernstein, Elliot R

    2011-09-01

    Electronically nonadiabatic processes such as ultrafast internal conversion (IC) from an upper electronic state (S(1)) to the ground electronic state (S(0)) though a conical intersection (CI), can play an essential role in the initial steps of the decomposition of energetic materials. Such nonradiative processes following electronic excitation can quench emission and store the excitation energy in the vibrational degrees of freedom of the ground electronic state. This excess vibrational energy in the ground electronic state can dissociate most of the chemical bonds of the molecule and can generate stable, small molecule products. The present study determines ultrafast IC dynamics of a model nitramine energetic material, dimethylnitramine (DMNA). Femtosecond (fs) pump-probe spectroscopy, for which a pump pulse at 271 nm and a probe pulse at 405.6 nm are used, is employed to elucidate the IC dynamics of this molecule from its S(1) excited state. A very short lifetime of the S(1) excited state (∼50 ± 16 fs) is determined for DMNA. Complete active space self-consistent field (CASSCF) calculations show that an (S(1)/S(0))(CI) CI is responsible for this ultrafast decay from S(1) to S(0). This decay occurs through a reaction coordinate involving an out-of-plane bending mode of the DMNA NO(2) moiety. The 271 nm excitation of DMNA is not sufficient to dissociate the molecule on the S(1) potential energy surface (PES) through an adiabatic NO(2) elimination pathway. PMID:21351779

  4. Hyaluroan-regulated lymphatic permeability through S1P receptors is crucial for cancer metastasis.

    PubMed

    Yu, Mengsi; He, Pingqing; Liu, Yiwen; He, Yiqing; Du, Yan; Wu, Man; Zhang, Guoliang; Yang, Cuixia; Gao, Feng

    2015-01-01

    Disruption of cancer lymphatic vessel barrier function occurs has been reported to involve in cancer lymphatic metastasis. Hyaluronan (HA), a major glycosaminoglycan component of the extracellular matrix, is associated with cancer metastasis. We investigated the effect of high/low molecular weight hyaluronan (HMW-HA/LMW-HA) on regulation of barrier function and tight junctions in cancer lymphatic endothelial cell (LEC) monolayer. Results showed that LMW-HA increased the permeability of cancer LEC monolayers and induced disruption of Zonula Occludens-1 (ZO-1)-mediated intercellular tight junction and actin stress fiber formation. HMW-HA treatment decreased permeability in cancer LEC monolayers and cortical actin ring formation. As reported, sphingosine 1-phosphate (S1P) receptors are involved in vascular integrity. After silencing of lymphatic vessel endothelial hyaluronan receptor (LYVE-1), upregulation of S1P receptors (S1P1 and S1P3) induced by HMW-HA/LMW-HA were inhibited, respectively. With S1P3 silenced, the disruption of ZO-1 as well as stress fiber formation and the ROCK1/RhoA signaling pathway induced by LMW-HA was not observed in cancer LEC. These results suggested that S1P receptors may play an important role in HMW-HA-/LMW-HA-mediated regulation of cancer lymphatic vessel integrity, which might be the initial step of cancer lymphatic metastasis and a useful intervention of cancer progression. PMID:25428387

  5. A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis

    PubMed Central

    Zhang, Lin; Orban, Martin; Lorenz, Michael; Barocke, Verena; Braun, Daniel; Urtz, Nicole; Schulz, Christian; von Brühl, Marie-Luise; Tirniceriu, Anca; Gaertner, Florian; Proia, Richard L.; Graf, Thomas; Bolz, Steffen-Sebastian; Montanez, Eloi; Prinz, Marco; Müller, Alexandra; von Baumgarten, Louisa; Billich, Andreas; Sixt, Michael; Fässler, Reinhard; von Andrian, Ulrich H.; Junt, Tobias

    2012-01-01

    Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood. The mechanisms that control platelet generation remain incompletely understood. Using conditional mutants and intravital multiphoton microscopy, we show here that the lipid mediator sphingosine 1-phosphate (S1P) serves as a critical directional cue guiding the elongation of megakaryocytic PP extensions from the interstitium into BM sinusoids and triggering the subsequent shedding of PPs into the blood. Correspondingly, mice lacking the S1P receptor S1pr1 develop severe thrombocytopenia caused by both formation of aberrant extravascular PPs and defective intravascular PP shedding. In contrast, activation of S1pr1 signaling leads to the prompt release of new platelets into the circulating blood. Collectively, our findings uncover a novel function of the S1P–S1pr1 axis as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia. PMID:23148237

  6. Photolabelling of mutant forms of the S1 subunit of pertussis toxin with NAD+.

    PubMed Central

    Cieplak, W; Locht, C; Mar, V L; Burnette, W N; Keith, J M

    1990-01-01

    The S1 subunit of pertussis toxin catalyses the hydrolysis of NAD+ (NAD+ glycohydrolysis) and the NAD(+)-dependent ADP-ribosylation of guanine-nucleotide-binding proteins. Recently, the S1 subunit of pertussis toxin was shown to be photolabelled by using radiolabelled NAD+ and u.v.; the primary labelled residue was Glu-129, thereby implicating this residue in the binding of NAD+. Studies from various laboratories have shown that the N-terminal portion of the S1 subunit, which shows sequence similarity to cholera toxin and Escherichia coli heat-labile toxin, is important to the maintenance of both glycohydrolase and transferase activity. In the present study the photolabelling technique was applied to the analysis of a series of recombinant-derived S1 molecules that possessed deletions or substitutions near the N-terminus of the S1 molecule. The results revealed a positive correlation between the extent of photolabelling with NAD+ and the magnitude of specific NAD+ glycohydrolase activity exhibited by the mutants. Enzyme kinetic analyses of the N-terminal mutants also identified a mutant with substantially reduced activity, a depressed photolabelling efficiency and a markedly increased Km for NAD+. The results support a direct role for the N-terminal region of the S1 subunit in the binding of NAD+, thereby providing a rationale for the effect of mutations in this region on enzymic activity. Images Fig. 1. PMID:2363691

  7. Design, Synthesis, and Biological Evaluation of Ganglioside Hp-s1 Analogues Varying at Glucosyl Moiety.

    PubMed

    Hung, Jung-Tung; Yeh, Chun-Hong; Yang, Shih-An; Lin, Chiu-Ya; Tai, Hung-Ju; Shelke, Ganesh B; Reddy, Daggula Mallikarjuna; Yu, Alice L; Luo, Shun-Yuan

    2016-08-17

    Ganglioside Hp-s1 is isolated from the ovary of sea urchin Diadema setosum. It exhibited better neuritogenic activity than GM1 in pheochromocytoma 12 cells. To explore the roles of glucosyl moiety of Hp-s1 in contributing to the neurogenic activity, we developed feasible procedures for synthesis of Hp-s1 analogues (2a-2f). The glucosyl moiety of Hp-s1 was replaced with α-glucose, α-galactose, β-galactose, α-mannose, and β-mannose, and their biological activities on SH-SY5Y cells and natural killer T (NKT) cells were evaluated. We found that the orientation of C-2 hydroxyl group at glucosyl moiety of Hp-s1 plays an important role to induce neurite outgrowth of SH-SY5Y cells. Surprisingly, compound 2d could activate NKT cells to produce interleukin 2, although it did not show great activity on neurite outgrowth of SH-SY5Y cells. In general, the Hp-s1 might be considered as a lead compound for the development of novel drugs aimed at modulating the activity of neuronal cells. PMID:27276519

  8. The Effects of Spinopelvic Parameters and Paraspinal Muscle Degeneration on S1 Screw Loosening

    PubMed Central

    Kim, Jin-Bum; Lee, Young-Seok; Nam, Taek-Kyun; Park, Yong-Sook; Kim, Young-Baeg

    2015-01-01

    Objective To investigate risk factors for S1 screw loosening after lumbosacral fusion, including spinopelvic parameters and paraspinal muscles. Methods We studied with 156 patients with degenerative lumbar disease who underwent lumbosacral interbody fusion and pedicle screw fixation including the level of L5-S1 between 2005 and 2012. The patients were divided into loosening and non-loosening groups. Screw loosening was defined as a halo sign larger than 1 mm around a screw. We checked cross sectional area of paraspinal muscles, mean signal intensity of the muscles on T2 weight MRI as a degree of fatty degeneration, spinopelvic parameters, bone mineral density, number of fusion level, and the characteristic of S1 screw. Results Twenty seven patients showed S1 screw loosening, which is 24.4% of total. The mean duration for S1 screw loosening was 7.3±4.1 months after surgery. Statistically significant risk factors were increased age, poor BMD, 3 or more fusion levels (p<0.05). Among spinopelvic parameters, a high pelvic incidence (p<0.01), a greater difference between pelvic incidence and lumbar lordotic angle preoperatively (p<0.01) and postoperatively (p<0.05). Smaller cross-sectional area and high T2 signal intensity in both multifidus and erector spinae muscles were also significant muscular risk factors (p<0.05). Small converging angle (p<0.001) and short intraosseous length (p<0.05) of S1 screw were significant screw related risk factors (p<0.05). Conclusion In addition to well known risk factors, spinopelvic parameters and the degeneration of paraspinal muscles also showed significant effects on the S1 screw loosening. PMID:26587190

  9. Phase I study of postoperative radiotherapy concurrent with S-1 in patients with gastric cancer.

    PubMed

    Qiu, Meng; Peng, Xing-chen; Bi, Feng; Wang, Xin; Li, Qiu; Xu, Feng; Li, Zhi-ping; Shen, Ya-li; Liu, Ji-yan; Zhao, Ya-qing; Cao, Dan; Gou, Hong-feng; Yang, Yu; Chen, Ye; Yi, Cheng

    2015-07-01

    Postoperative chemoradiotherapy (CRT) with concurrent 5-fluorouracil is the standard care for gastric cancer patients after curative surgery. The previous studies revealed that the subgroup of patients with high recurrence risk would benefit most from adjuvant CRT. S-1, a novel oral fluorouracil, has showed very effective in metastatic gastric cancer and became the standard option for gastric cancer with D2 dissection. The safety and dosage of S-1 combined with postoperative radiotherapy have not yet been evaluated. This study is to determine the maximum tolerate dose (MTD) and dose-limiting toxicity (DLT) of S-1 given concurrently with postoperative high-dose radiotherapy in gastric cancer. Patients with more advanced stage (pT4 and/or pN+) after R0 resection were recruited. Eligible patients received one cycle standard SOX (S-1 plus oxaliplatin) chemotherapy, then S-1 monotherapy with concurrent radiotherapy for 6 weeks, followed by additional three cycles of SOX. During the concurrent CRT, S-1 was administered on every radiotherapy treatment day according to a predefined dose-escalation schedule. Radiotherapy (3D-RT or IMRT) was given to a total dose of 50.4 Gy in 28 fractions. DLT was defined as grade 3 or 4 hematologic and non-hematologic toxicity. From March 2011 to October 2012, 21 patients were enrolled at five dose levels: 40 (n = 3), 50 (n = 3), 60 (n = 6), 70 (n = 6) and 80 mg/m(2)/day (n = 3). D2-dissection was performed in 18 patients (85.7 %) and 15 patients (71.4 %) had stage III disease. The most common dose-related toxicity was anorexia, nausea and vomiting, fatigue and leucopenia. DLT was occurred in one patient at 60 mg/m(2)/day (grade 3 fatigue), one patient at 70 mg/m(2)/day (grade 3 vomiting and anorexia), two patients at 80 mg/m(2)/day (one with grade 3 vomiting and anorexia; another with grade 3 febrile leucopenia). Four patients did not complete CRT as planned. Overall, this phase I study demonstrated that postoperative CRT with daily S-1

  10. Identification of genetic polymorphisms of CYP2S1 in a Finnish Caucasian population.

    PubMed

    Saarikoski, Sirkku T; Suitiala, Tuula; Holmila, Reetta; Impivaara, Olli; Järvisalo, Jorma; Hirvonen, Ari; Husgafvel-Pursiainen, Kirsti

    2004-10-01

    CYP2S1 is a recently discovered member of the cytochrome P450 (CYP) gene superfamily. Interestingly, even though the DNA sequence identifies it as the sole member of the new CYP2S family, CYP2S1 exhibits many features typical to CYP1 family members, e.g. dioxin-inducibility mediated by the aryl hydrocarbon receptor (AHR) and the aryl hydrocarbon receptor nuclear translocator (ARNT). In addition, CYP2S1 metabolises some aromatic hydrocarbons as well as cellular substances. These characteristics, together with a wide extrahepatic tissue distribution, suggest that CYP2S1 may have an important role in both exogenous and endogenous metabolism. This is the first study characterising CYP2S1 alleles and naming them with the recommended CYP allele nomenclature. We used denaturing gradient gel electrophoresis (DGGE) and direct sequencing to investigate genetic variation of CYP2S1 in 100 male Finnish Caucasians. Those exons in which variation was found were examined in subsequent 100 subjects. The coding region of all of the nine exons, as well as a 449 bp fragment of the proximal promoter region, was analysed. This systematic investigation revealed eight single nucleotide polymorphisms (SNPs), which comprise nine different variant alleles (haplotypes), in addition to the wild-type allele. Seven of the SNPs occurred in the protein-coding areas and one in the proximal 3' untranslated region (3'UTR). Two of these sequence variations (10347C > T and 13106C > T) result in non-conservative amino acid substitutions, i.e. Arg380Cys and Pro466Leu, respectively. The respective allelic variants, CYP2S1*2 ([10347C > T]) and CYP2S1*3 (13106C > T; 13255A > G]), occurred in our study population at frequencies of 0.50 and 3.75%, respectively. The most common of the variant alleles was CYP2S1*1H (23.8%), harbouring a 13255A > G substitution located in the 3'UTR. PMID:15450424

  11. Short-range correlations and the 3 s1 /2 wave function in 206Pb

    NASA Astrophysics Data System (ADS)

    Anders, M. R.; Shlomo, S.; Talmi, I.

    2015-09-01

    The charge-density difference between 206Pb and 205Tl , measured by elastic electron scattering, offers a unique opportunity to look for effects of short-range correlations on a shell-model wave function of a single proton. The measured difference is very similar to the charge density due to a proton in a 3 s1 /2 orbit. If there is a potential whose 3 s1 /2 wave function yields the measured difference between the charge distributions, no effect of short-range correlations is evident. To check this point, we look for a potential whose 3 s1 /2 wave function yields the measured data. We developed a novel method to obtain the potential directly from the density and its first and second derivatives. Fits to parametrized potentials were also carried out. The 3 s1 /2 wave functions of the potentials determined here reproduce fairly well the experimental data within the quoted errors. To detect possible effects of two-body correlations on the 3 s1 /2 shell-model wave function, more accurate measurements are required.

  12. Renormalized Traces and Cocycles on the Algebra of S 1-Pseudo-differential Operators

    NASA Astrophysics Data System (ADS)

    Magnot, Jean-Pierre

    2006-02-01

    Using renormalized (or weighted) traces of classical pseudo-differential operators and calculus on formal symbols. We exhibit three cocycles on the Lie algebra of classical pseudo-differential operators Cl(S^1,mathbb{C}^n) acting on L^2(S^1,mathbb{C}^n). We first show that the Schwinger functional c_S^D associated to the Dirac operator is a cocycle on Cl(S^1,mathbb{C}^n), and not only on a restricted algebra Cl(S^1,mathbb{C}^n)^D_res. Then, we investigate two bilinear functionals c+^D and c_{++}^D, which satisfies {1 over 2}c_S^D = c_+^D - c_{++}^D. We show that c+^D and c_{++}^D are two cocycles in Cl(S^1,mathbb{C}^n), and {1 over 2}c_S^D and c_+^D have the same nonvanishing cohomology class. We finaly calculate c+^D on classical pseudo-differential operators of order 1 and on differential operators of order 1, in terms of partial symbols. By this last computation, we recover the Virasoro cocyle and the Kähler form of the loop group.

  13. Novel S1P1 receptor agonists - Part 4: Alkylaminomethyl substituted aryl head groups.

    PubMed

    Lescop, Cyrille; Müller, Claus; Mathys, Boris; Birker, Magdalena; de Kanter, Ruben; Kohl, Christopher; Hess, Patrick; Nayler, Oliver; Rey, Markus; Sieber, Patrick; Steiner, Beat; Weller, Thomas; Bolli, Martin H

    2016-06-30

    In a previous communication we reported on the discovery of alkylamino pyridine derivatives (e.g. 1) as a new class of potent, selective and efficacious S1P1 receptor (S1PR1) agonists. However, more detailed profiling revealed that this compound class is phototoxic in vitro. Here we describe a new class of potent S1PR1 agonists wherein the exocyclic nitrogen was moved away from the pyridine ring (e.g. 11c). Further structural modifications led to the identification of novel alkylaminomethyl substituted phenyl and thienyl derivatives as potent S1PR1 agonists. These new alkylaminomethyl aryl compounds showed no phototoxic potential. Based on their in vivo efficacy and ability to penetrate the brain, the 5-alkyl-aminomethyl thiophenes appeared to be the most interesting class. Potent and selective S1PR1 agonist 20e, for instance, maximally reduced the blood lymphocyte count (LC) for 24 h after oral administration of 10 mg/kg to rat and its brain concentrations reached >500 ng/g over 24 h. PMID:27061986

  14. Efficient Inhibition of Hepatitis B Virus Infection by a preS1-binding Peptide.

    PubMed

    Ye, Xiaoli; Zhou, Ming; He, Yonggang; Wan, Yanmin; Bai, Weiya; Tao, Shuai; Ren, Yanqin; Zhang, Xinxin; Xu, Jianqing; Liu, Jing; Zhang, Junqi; Hu, Kanghong; Xie, Youhua

    2016-01-01

    Entry inhibitors are promising novel antivirals against hepatitis B virus (HBV) infection. The existing potential entry inhibitors have targeted the cellular receptor(s). In this study, we aim to develop the first entry inhibitor that inhibits HBV infection via targeting viral particles. The preS1 segment of the large envelope glycoprotein of HBV is essential for virion attachment and infection. Previously, we obtained a preS1-binding short peptide B10 by screening a phage display peptide library using the N-terminal half of preS1 (residues 1 to 60, genotype C). We report here that by means of concatenation of B10, we identified a quadruple concatemer 4B10 that displayed a markedly increased preS1-binding activity. The main binding site of 4B10 in preS1 was mapped to the receptor binding enhancing region. 4B10 blocked HBV attachment to hepatic cells and inhibited HBV infection of primary human and tupaia hepatocytes at low nanomolar concentrations. The 4B10-mediated inhibition of HBV infection is specific as it did not inhibit the infection of vesicular stomatitis virus glycoprotein pseudotyped lentivirus or human immunodeficiency virus type 1. Moreover, 4B10 showed no binding activity to hepatic cells. In conclusion, we have identified 4B10 as a promising candidate for a novel class of HBV entry inhibitors. PMID:27384014

  15. S1 pocket of glutamate carboxypeptidase II: a new binding site for amyloid-β degradation.

    PubMed

    Lee, Suk Kyung; Kim, Hyunyoung; Cheong, You-Hoon; Kim, Min-Ju; Jo, Sangmee Ahn; Youn, Hyung-Seop; Park, Sang Ick

    2013-09-01

    We recently reported that glutamate carboxypeptidase II (GCPII) has a new physiological function degrading amyloid-β (Aβ), distinct from its own hydrolysis activity in N-acetyl-L-aspartyl-L-glutamate (NAAG); however, its underlying mechanism remains undiscovered. Using site-directed mutagenesis and S1 pocket-specific chemical inhibitor (compound 2), which was developed for the present study based on in sillico computational modeling, we discovered that the Aβ degradation occurs through S1 pocket but not through S1' pocket responsible for NAAG hydrolysis. Treatment with compound 2 prevented GCPII from Aβ degradation without any impairment in NAAG hydrolysis. Likewise, 2-PMPA (specific GCPII inhibitor developed targeting S1' pocket) completely blocked the NAAG hydrolysis without any effect on Aβ degradation. Pre-incubation with NAAG and Aβ did not affect Aβ degradation and NAAG hydrolysis, respectively. These data suggest that GCPII has two distinctive binding sites for two different substrates and that Aβ degradation occurs through binding to S1 pocket of GCPII. PMID:23891752

  16. Efficient Inhibition of Hepatitis B Virus Infection by a preS1-binding Peptide

    PubMed Central

    Ye, Xiaoli; Zhou, Ming; He, Yonggang; Wan, Yanmin; Bai, Weiya; Tao, Shuai; Ren, Yanqin; Zhang, Xinxin; Xu, Jianqing; Liu, Jing; Zhang, Junqi; Hu, Kanghong; Xie, Youhua

    2016-01-01

    Entry inhibitors are promising novel antivirals against hepatitis B virus (HBV) infection. The existing potential entry inhibitors have targeted the cellular receptor(s). In this study, we aim to develop the first entry inhibitor that inhibits HBV infection via targeting viral particles. The preS1 segment of the large envelope glycoprotein of HBV is essential for virion attachment and infection. Previously, we obtained a preS1-binding short peptide B10 by screening a phage display peptide library using the N-terminal half of preS1 (residues 1 to 60, genotype C). We report here that by means of concatenation of B10, we identified a quadruple concatemer 4B10 that displayed a markedly increased preS1-binding activity. The main binding site of 4B10 in preS1 was mapped to the receptor binding enhancing region. 4B10 blocked HBV attachment to hepatic cells and inhibited HBV infection of primary human and tupaia hepatocytes at low nanomolar concentrations. The 4B10-mediated inhibition of HBV infection is specific as it did not inhibit the infection of vesicular stomatitis virus glycoprotein pseudotyped lentivirus or human immunodeficiency virus type 1. Moreover, 4B10 showed no binding activity to hepatic cells. In conclusion, we have identified 4B10 as a promising candidate for a novel class of HBV entry inhibitors. PMID:27384014

  17. Novel S1P(1) receptor agonists--part 3: from thiophenes to pyridines.

    PubMed

    Bolli, Martin H; Abele, Stefan; Birker, Magdalena; Bravo, Roberto; Bur, Daniel; de Kanter, Ruben; Kohl, Christopher; Grimont, Julien; Hess, Patrick; Lescop, Cyrille; Mathys, Boris; Müller, Claus; Nayler, Oliver; Rey, Markus; Scherz, Michael; Schmidt, Gunther; Seifert, Jürgen; Steiner, Beat; Velker, Jörg; Weller, Thomas

    2014-01-01

    In preceding communications we summarized our medicinal chemistry efforts leading to the identification of potent, selective, and orally active S1P1 agonists such as the thiophene derivative 1. As a continuation of these efforts, we replaced the thiophene in 1 by a 2-, 3-, or 4-pyridine and obtained less lipophilic, potent, and selective S1P1 agonists (e.g., 2) efficiently reducing blood lymphocyte count in the rat. Structural features influencing the compounds' receptor affinity profile and pharmacokinetics are discussed. In addition, the ability to penetrate brain tissue has been studied for several compounds. As a typical example for these pyridine based S1P1 agonists, compound 53 showed EC50 values of 0.6 and 352 nM for the S1P1 and S1P3 receptor, respectively, displayed favorable PK properties, and penetrated well into brain tissue. In the rat, compound 53 maximally reduced the blood lymphocyte count for at least 24 h after oral dosing of 3 mg/kg. PMID:24367923

  18. Novel S1P1 receptor agonists - Part 5: From amino-to alkoxy-pyridines.

    PubMed

    Bolli, Martin H; Lescop, Cyrille; Birker, Magdalena; de Kanter, Ruben; Hess, Patrick; Kohl, Christopher; Nayler, Oliver; Rey, Markus; Sieber, Patrick; Velker, Jörg; Weller, Thomas; Steiner, Beat

    2016-06-10

    In a previous communication we reported on the discovery of aminopyridine 1 as a potent, selective and orally active S1P1 receptor agonist. More detailed studies revealed that this compound is phototoxic in vitro. As a result of efforts aiming at eliminating this undesired property, a series of alkoxy substituted pyridine derivatives was discovered. The photo irritancy factor (PIF) of these alkoxy pyridines was significantly lower than the one of aminopyridine 1 and most compounds were not phototoxic. Focused SAR studies showed, that 2-, 3-, and 4-pyridine derivatives delivered highly potent S1P1 receptor agonists. While the 2-pyridines were clearly more selective against S1PR3, the corresponding 3- or 4-pyridine analogues showed significantly longer oral half-lives and as a consequence longer pharmacological duration of action after oral administration. One of the best compounds, cyclopentoxy-pyridine 45b lacked phototoxicity, showed EC50 values of 0.7 and 140 nM on S1PR1 and S1PR3, respectively, and maximally reduced the blood lymphocyte count for at least 24 h after oral administration of 10 mg/kg to Wistar rats. PMID:27027817

  19. An oral fluoropyrimidine agent S-1 induced interstitial lung disease: A case report

    PubMed Central

    Yamane, Hiromichi; Kinugawa, Masahide; Umemura, Shigeki; Shiote, Yasuhiro; Kudo, Kenichiro; Suwaki, Toshimitsu; Kamei, Haruhito; Takigawa, Nagio; Kiura, Katsuyuki

    2011-01-01

    A 66-year-old Japanese man with pancreatic cancer received eleven courses of gemcitabine monotherapy. The tumor responded to gemcitabine until metastatic liver tumors progressed. Subsequently, he was treated with S-1, an oral fluoropyrimidine anticancer agent, as salvage chemotherapy. Forty-two days after initiating S-1, he presented with dyspnea and fever. Chest computed tomography showed diffuse interstitial lesions with thickening of the alveolar septa and ground glass opacity. Serum KL-6 level was elevated to 1,230 U/mL and he did not use any other drugs except insulin. Thus, the development of interstitial lung disease (ILD) was considered to be due to S-1. Arterial blood oxygen pressure was 49.6 Torr in spite of oxygen administration (5 L/min). Steroid therapy improved his symptoms and the interstitial shadows on chest radiograph. Although S-1-induced ILD has mostly been reported to be mild, clinicians should be aware that S-1 has the potential to cause fatal ILD. PMID:21773080

  20. A search for the H2 /3, 0/ S1 line in the spectrum of Titan

    NASA Technical Reports Server (NTRS)

    Muench, G.; Trauger, J. T.; Roesler, F. L.

    1977-01-01

    Results are reported for measurements of the quadrupole S1 line of the (3, 0) absorption band of H2 in spectra of Titan, which were performed at an effective resolution of 0.09 A by scanning with a PEPSIOS spectrometer over a range of 0.85 A centered at the expected position of the investigated line and sampling in 80 contiguous channels. No statistically significant H2 (3, 0) S1 feature is found in the spectra, but a three-sigma upper limit of 3 mA is set for the equivalent width of the S1 line that might be present in a co-added spectrum. It is concluded that these measurements do not provide any evidence for the presence of H2 in the atmosphere of Titan.

  1. The 2(2S + 1)-formalism and its connection with other descriptions

    NASA Astrophysics Data System (ADS)

    Dvoeglazov, Valeriy V.

    2016-02-01

    In the framework of the Joos-Weinberg 2(2S + 1)-theory for massless particles, the dynamical invariants have been derived from the Lagrangian density which is considered to be a 4-vector. A la Majorana interpretation of the 6-component “spinors”, the field operators of S = 1 particles, as the left- and right-circularly polarized radiation, leads us to the conserved quantities which are analogous to those obtained by Lipkin and Sudbery. The scalar Lagrangian of the Joos-Weinberg theory is shown to be equivalent to the Lagrangian of a free massless field, introduced by Hayashi. As a consequence of a new “gauge” invariance this skew-symmetric field describes physical particles with the longitudinal components only. The interaction of the spinor field with the Weinberg’s 2(2S + 1)-component massless field is considered. New interpretation of the Weinberg field function is proposed.

  2. Use of S1 nuclease in deep sequencing for detection of double-stranded RNA viruses.

    PubMed

    Shimada, Saya; Nagai, Makoto; Moriyama, Hiromitsu; Fukuhara, Toshiyuki; Koyama, Satoshi; Omatsu, Tsutomu; Furuya, Tetsuya; Shirai, Junsuke; Mizutani, Tetsuya

    2015-09-01

    Metagenomic approach using next-generation DNA sequencing has facilitated the detection of many pathogenic viruses from fecal samples. However, in many cases, majority of the detected sequences originate from the host genome and bacterial flora in the gut. Here, to improve efficiency of the detection of double-stranded (ds) RNA viruses from samples, we evaluated the applicability of S1 nuclease on deep sequencing. Treating total RNA with S1 nuclease resulted in 1.5-28.4- and 10.1-208.9-fold increases in sequence reads of group A rotavirus in fecal and viral culture samples, respectively. Moreover, increasing coverage of mapping to reference sequences allowed for sufficient genotyping using analytical software. These results suggest that library construction using S1 nuclease is useful for deep sequencing in the detection of dsRNA viruses. PMID:25843154

  3. Radiationless deactivation of 6-aminocoumarin from the S1-ICT state in nonspecifically interacting solvents.

    PubMed

    Krystkowiak, Ewa; Dobek, Krzysztof; Burdziński, Gotard; Maciejewski, Andrzej

    2012-08-01

    This paper presents the results of a spectral (absorption and emission) and photophysical study of 6-aminocoumarin (6AC) in the solvents with which this molecule interacts only nonspecifically (n-alkanes, tetrachloromethane and 1-chloro-n-alkanes) and in nitriles. The strong effects of the solvents on the emission spectra, fluorescence quantum yield and lifetime of 6AC were observed. The results of the steady-state and time-resolved photophysical study suggest the presence of very fast nonradiative deactivation processes. It is concluded that besides fluorescence, the efficient S(1)-ICT → S(0) internal conversion in nonpolar aprotic solvents arises from vibronic interactions between close-lying S(1)-ICT(π,π*) and S(2)(n,π*) states. Moreover, unexpectedly efficient triplet state formation occurs. In nitriles the intermolecular hydrogen-bonding interactions with solvent molecules also facilitate the nonradiative decay process involving the S(1)-exciplex. PMID:22622372

  4. Combination chemotherapy with S-1 and docetaxel for cutaneous angiosarcoma resistant to paclitaxel.

    PubMed

    Kajihara, Ikko; Kanemaru, Hisashi; Miyake, Taiga; Aoi, Jun; Masuguchi, Shinichi; Fukushima, Satoshi; Jinnin, Masatoshi; Ihn, Hironobu

    2015-02-01

    The prognosis of cutaneous angiosarcoma is very poor compared with that of other skin malignancies. The main reason for this is the limited regimens of chemotherapy available for angiosarcoma, because it is resistant to most common chemotherapeutic agents. Therefore, there is an urgent need to identify new treatment options. Recently, S-1 and docetaxel therapy was reported to be effective for advanced gastric cancer and metastatic extramammary Paget's disease. Therefore, we treated paclitaxel-resistant angiosarcoma patient with S-1/docetaxel chemotherapy. The progression-free survival was 5.0 months although grade 3 adverse events such as diarrhea and neutropenia developed. Our data need to be confirmed in a large number of patients, but S-1/docetaxel chemotherapy as an additional regimen seems to be an effective treatment option for paclitaxel-resistant angiosarcoma. PMID:25788055

  5. Molecular and immunological characterization of the glycosylated orange allergen Cit s 1.

    PubMed

    Pöltl, Gerald; Ahrazem, Oussama; Paschinger, Katharina; Ibañez, M Dolores; Salcedo, Gabriel; Wilson, Iain B H

    2007-02-01

    The IgE of sera from patients with a history of allergy to oranges (Citrus sinensis) binds a number of proteins in orange extract, including Cit s 1, a germin-like protein. In the present study, we have analyzed its immunological cross-reactivity and its molecular nature. Sera from many of the patients examined recognize a range of glycoproteins and neoglycoconjugates containing beta1,2-xylose and core alpha1,3-fucose on their N-glycans. These reagents also inhibited the interaction of Cit s 1 with patients' sera, thus underlining the critical role of glycosylation in the recognition of this protein by patients' IgE and extending previous data showing that deglycosylated Cit s 1 does not possess IgE epitopes. In parallel, we examined the peptide sequence and glycan structure of Cit s 1, using mass spectrometric techniques. Indeed, we achieved complete sequence coverage of the mature protein compared with the translation of an expressed sequence tag cDNA clone and demonstrated that the single N-glycosylation site of this protein carries oligosaccharides with xylose and fucose residues. Owing to the presumed requirement for multivalency for in vivo allergenicity, our molecular data showing that Cit s 1 is monovalent as regards glycosylation and that the single N-glycan is the target of the IgE response to this protein explain the immunological cross-reactive properties of Cit s 1 as well as its equivocal nature as a clinically relevant allergen. PMID:17095532

  6. Optimization of a Potent, Orally Active S1P1 Agonist Containing a Quinolinone Core

    PubMed Central

    2011-01-01

    The optimization of a series of S1P1 agonists with limited activity against S1P3 is reported. A polar headgroup was used to improve the physicochemical and pharmacokinetic parameters of lead quinolinone 6. When dosed orally at 1 and 3 mg/kg, the azahydroxymethyl analogue 22 achieved statistically significant lowering of circulating blood lymphocytes 24 h postdose. In rats, a dose-proportional increase in exposure was measured when 22 was dosed orally at 2 and 100 mg/kg. PMID:24900374

  7. STS-112 S1 truss in Payload Changeout Room at Launch Pad 39-B

    NASA Technical Reports Server (NTRS)

    2002-01-01

    KENNEDY SPACE CENTER, FLA. -- In the Payload Changeout Room at the pad, the payload is moved out of the payload canister for transfer to Space Shuttle Atlantis' payload bay for mission STS-112. The primary payload on the mission is the S1 Integrated Truss Structure. The first starboard truss segment, the S1 will be attached to the Central truss segment, the S0 Truss, on the International Space Station during the mission. Atlantis is scheduled to launch no earlier than Oct. 2.

  8. Negative infrared photoconductivity in CdS1-xSex films

    NASA Astrophysics Data System (ADS)

    Abdinov, A. S.; Jafarov, M. A.; Mamedov, H. M.; Nasirov, E. F.

    2003-09-01

    The negative infrared photoconductivity (NPH) has been observed for the first time in CdS1-xSex films, in the wavelength region of 0.700 - 1.23 μm. at values of stimulating light intensity Φ = 100 - 400 Lk. electrical field E = 0.5 - 130 V/cm and temperature T = 265 - 310 Κ. It is established, that basic laws of NPH explains on the basis of two-barrier model and in the considered conditions a charge carriers, overcome a barrier by tunneling. A films of CdS1-xSex can be used in IR engineering and negatronics.

  9. 11-cis retinal torsion: A QTAIM and stress tensor analysis of the S1 excited state

    NASA Astrophysics Data System (ADS)

    Maza, Julio R.; Jenkins, Samantha; Kirk, Steven R.

    2016-05-01

    We investigate torsion about the C11-C12 bond mid-point for the S1 state of 11-cis retinal, using a QTAIM and stress tensor analysis. The QTAIM and stress tensor responses to a torsion ±α increase at a faster rate for the preferred direction of torsion though the CI seam. A QTAIM and stress tensor vector-based analysis provides an alternative way of characterising the asymmetry of the S1 potential energy surface. In the vicinity of the CI seam the ellipticity ε attained minimum values. The application of this analysis to molecular rotary motors is briefly discussed.

  10. Observation of an exotic S = +1 baryon in exclusive photoproduction from the deuteron.

    PubMed

    Stepanyan, S; Hicks, K; Carman, D S; Pasyuk, E; Schumacher, R A; Smith, E S; Tedeschi, D J; Todor, L; Adams, G; Ambrozewicz, P; Anciant, E; Anghinolfi, M; Asavapibhop, B; Audit, G; Avakian, H; Bagdasaryan, H; Ball, J P; Barrow, S P; Battaglieri, M; Beard, K; Bektasoglu, M; Bellis, M; Berman, B L; Bianchi, N; Biselli, A S; Boiarinov, S; Bouchigny, S; Bradford, R; Branford, D; Briscoe, W J; Brooks, W K; Burkert, V D; Butuceanu, C; Calarco, J R; Carnahan, B; Chen, S; Ciciani, L; Cole, P L; Coleman, A; Cords, D; Corvisiero, P; Crabb, D; Crannell, H; Cummings, J P; De Sanctis, E; Degtyarenko, P V; Denizli, H; Dennis, L; De Vita, R; Dharmawardane, K V; Dhuga, K S; Djalali, C; Dodge, G E; Doughty, D; Dragovitsch, P; Dugger, M; Dytman, S; Dzyubak, O P; Egiyan, H; Egiyan, K S; Elouadrhiri, L; Empl, A; Eugenio, P; Fatemi, R; Feuerbach, R J; Ficenec, J; Forest, T A; Funsten, H; Garçon, M; Gavalian, G; Gilfoyle, G P; Giovanetti, K L; Gordon, C I O; Gothe, R; Griffioen, K; Guidal, M; Guillo, M; Guo, L; Gyurjyan, V; Hadjidakis, C; Hakobyan, R S; Hardie, J; Heddle, D; Heimberg, P; Hersman, F W; Hicks, R S; Holtrop, M; Hu, J; Hyde-Wright, C E; Ito, M M; Jenkins, D; Joo, K; Juengst, H G; Kellie, J D; Khandaker, M; Kim, K Y; Kim, K; Kim, W; Klein, A; Klein, F J; Klimenko, A V; Klusman, M; Kossov, M; Kramer, L H; Kuang, Y; Kubarovsky, V; Kuhn, S E; Kuhn, J; Lachniet, J; Lawrence, D; Li, J; Lima, A; Livingston, K; Lukashin, K; Manak, J J; McAleer, S; McNabb, J W C; Mecking, B A; Mehrabyan, S; Melone, J J; Mestayer, M D; Meyer, C A; Mikhailov, K; Minehart, R; Mirazita, M; Miskimen, R; Mokeev, V; Morand, L; Morrow, S; Muccifora, V; Mueller, J; Murphy, L Y; Mutchler, G S; Napolitano, J; Nasseripour, R; Niccolai, S; Niculescu, G; Niculescu, I; Niczyporuk, B B; Niyazov, R A; Nozar, M; O'Brien, J; O'Rielly, G V; Opper, A K; Osipenko, M; Park, K; Peterson, G; Philips, S A; Pivnyuk, N; Pocanic, D; Pogorelko, O; Polli, E; Pozdniakov, S; Preedom, B M; Price, J W; Prok, Y; Protopopescu, D; Qin, L M; Raue, B A; Riccardi, G; Ricco, G; Ripani, M; Ritchie, B G; Ronchetti, F; Rossi, P; Rowntree, D; Rubin, P; Sabatié, F; Salgado, C; Santoro, J; Sapunenko, V; Serov, V S; Sharabian, Y G; Shaw, J; Simionatto, S; Skabelin, A V; Smith, L C; Sober, D I; Strakovsky, I I; Stavinsky, A; Stoler, P; Suleiman, R; Taiuti, M; Taylor, S; Thoma, U; Thompson, R; Tur, C; Ungaro, M; Vineyard, M F; Vlassov, A V; Wang, K; Weinstein, L B; Weller, H; Weygand, D P; Whisnant, C S; Wolin, E; Wood, M H; Yegneswaran, A; Yun, J

    2003-12-19

    In an exclusive measurement of the reaction gammad-->K(+)K(-)pn, a narrow peak that can be attributed to an exotic baryon with strangeness S=+1 is seen in the K(+)n invariant mass spectrum. The peak is at 1.542+/-0.005 GeV/c(2) with a measured width of 0.021 GeV/c(2) FWHM, which is largely determined by experimental mass resolution. The statistical significance of the peak is (5.2+/-0.6)sigma. The mass and width of the observed peak are consistent with recent reports of a narrow S=+1 baryon by other experimental groups. PMID:14754107

  11. S1P3 receptor influences key physiological properties of fast-twitch extensor digitorum longus muscle.

    PubMed

    Germinario, Elena; Bondì, Michela; Cencetti, Francesca; Donati, Chiara; Nocella, Marta; Colombini, Barbara; Betto, Romeo; Bruni, Paola; Bagni, Maria Angela; Danieli-Betto, Daniela

    2016-06-01

    To examine the role of sphingosine 1-phosphate (S1P) receptor 3 (S1P3) in modulating muscle properties, we utilized transgenic mice depleted of the receptor. Morphological analyses of extensor digitorum longus (EDL) muscle did not show evident differences between wild-type and S1P3-null mice. The body weight of 3-mo-old S1P3-null mice and the mean cross-sectional area of transgenic EDL muscle fibers were similar to those of wild-type. S1P3 deficiency enhanced the expression level of S1P1 and S1P2 receptors mRNA in S1P3-null EDL muscle. The contractile properties of S1P3-null EDL diverge from those of wild-type, largely more fatigable and less able to recover. The absence of S1P3 appears responsible for a lower availability of calcium during fatigue. S1P supplementation, expected to stimulate residual S1P receptors and signaling, reduced fatigue development of S1P3-null muscle. Moreover, in the absence of S1P3, denervated EDL atrophies less than wild-type. The analysis of atrophy-related proteins in S1P3-null EDL evidences high levels of the endogenous regulator of mitochondria biogenesis peroxisome proliferative-activated receptor-γ coactivator 1α (PGC-1α); preserving mitochondria could protect the muscle from disuse atrophy. In conclusion, the absence of S1P3 makes the muscle more sensitive to fatigue and slows down atrophy development after denervation, indicating that S1P3 is involved in the modulation of key physiological properties of the fast-twitch EDL muscle. PMID:26718782

  12. Effect of Self-Regulated Learning and Motivation to Achieve against Teacher Professional Capability for Student S1 PGSD of Science Field Compared with Regular Student S1 PGSD at UPBJJ Serang

    ERIC Educational Resources Information Center

    Prayekti

    2015-01-01

    This study is to know effect of self-regulated learning and motivation to achieve against teacher professional capability for student S1 PGSD of science field compared with regular student S1 PGSD. The student uses grades of Classroom Action Research (CAR) and Stabilization of Professional Capability (SPC) on curriculum of S1 PGSD to see…

  13. Wavelength-tunable lasing in single-crystal CdS1-XSeX nanoribbons

    NASA Astrophysics Data System (ADS)

    Liu, Y. K.; Zapien, J. A.; Shan, Y. Y.; Tang, H.; Lee, C. S.; Lee, S. T.

    2007-09-01

    Alloyed ternary CdS1-XSeX nanoribbons of variable composition X were synthesized by the combination of thermal evaporation and laser ablation. High-resolution transmission electron microscopy and x-ray diffraction showed that the ternary CdS1-XSeX nanoribbons were single phase and highly crystalline. Room-temperature optical measurements showed that band-gap engineering could be realized in CdS1-XSeX nanoribbons via modulation in composition X. Lasing emission between the band-gap energy of CdS (512 nm) and that of CdSe (710 nm) was observed for composition 0S1-XSeX nanoribbons reveal the uniform optical properties of the nanoribbons, which supports the absence of phase segregation within the nanoribbon. Fine tuning of the lasing wavelength via composition changes is shown to be smaller than 0.1 nm, and is capable of overlapping thermally induced tuning, demonstrating the possibility of continuous tuning in the lasing wavelength. The broad and fine tunable lasing properties of ternary nanoribbons have potential applications in color-tuned nanolasers, biological labels, and nano-optoelectronics.

  14. Sacrum fracture following L5-S1 stand-alone interbody fusion for isthmic spondylolisthesis.

    PubMed

    Phan, Kevin; Mobbs, Ralph J

    2015-11-01

    We report a 72-year-old man with a rare sacral fracture following stand-alone L5-S1 anterior lumbar interbody fusion for isthmic spondylolisthesis. The man underwent a minimally invasive management strategy using posterior percutaneous pedicle fixation and partial reduction of the deformity. We also discuss the current literature on fusion procedures for isthmic spondylolisthesis. PMID:26100158

  15. SKI-1/S1P inhibitor PF-429242 impairs the onset of HCV infection.

    PubMed

    Blanchet, Matthieu; Sureau, Camille; Guévin, Carl; Seidah, Nabil G; Labonté, Patrick

    2015-03-01

    Worldwide, approximately 170 million individuals are afflicted with chronic hepatitis C virus (HCV) infection. To prevent the development of inherent diseases such as cirrhosis and hepatocellular carcinoma, tremendous efforts have been made, leading to the development of promising new treatments. However, their efficiency is still dependent on the viral genotype. Additionally, these treatments that target the virus directly can trigger the emergence of resistant variants. In a previous study, we have demonstrated that a long-term (72h) inhibition of SKI-1/S1P, a master lipogenic pathway regulator through activation of SREBP, resulted in impaired HCV genome replication and infectious virion secretion. In the present study, we sought to investigate the antiviral effect of the SKI-1/S1P small molecule inhibitor PF-429242 at the early steps of the HCV lifecycle. Our results indicate a very potent antiviral effect of the inhibitor early in the viral lifecycle and that the overall action of the compound relies on two different contributions. The first one is SREBP/SKI-1/S1P dependent and involves LDLR and NPC1L1 proteins, while the second one is SREBP independent. Overall, our study confirms that SKI-1/S1P is a relevant target to impair HCV infection and that PF-429242 could be a promising candidate in the field of HCV infection treatment. PMID:25573299

  16. The 3P0-VERSUS 3S1-MODELS for Quark-Antiquark Annihilation

    NASA Astrophysics Data System (ADS)

    Green, A. M.; Niskanen, J. A.

    A comparison is made between the 3S1- and 3P0-models for quark-antiquark annihilation or creation. Even though the former appears, at first sight, to be superior for Nbar {N} annihilation into two mesons, it is argued from their effects in meson decays that this conclusion is premature.

  17. Installation of the S1 Truss to the International Space Station

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Astronauts Piers J. Sellers (left ) and David A. Wolf work on the newly installed Starboard One (S1) truss to the International Space Station (ISS) during the STS-112 mission. The primary payloads of this mission, ISS Assembly Mission 9A, were the Integrated Truss Assembly S1 (S One), the starboard side thermal radiator truss, and the Crew Equipment Translation Aid (CETA) cart to the ISS. The S1 truss provides structural support for the orbiting research facility's radiator panels, which use ammonia to cool the Station's complex power system. The S1 truss was attached to the S0 (S Zero) truss, which was launched on April 8, 2002 aboard the STS-110, and flows 637 pounds of anhydrous ammonia through three heat-rejection radiators. The truss is 45-feet long, 15-feet wide, 10-feet tall, and weighs approximately 32,000 pounds. The CETA cart was attached to the Mobil Transporter and will be used by assembly crews on later missions. Manufactured by the Boeing Company in Huntington Beach, California, the truss primary structure was transferred to the Marshall Space Flight Center in February 1999 for hardware installations and manufacturing acceptance testing. The launch of the STS-112 mission occurred on October 7, 2002, and its 11-day mission ended on October 18, 2002.

  18. 26 CFR 1.6050S-1 - Information reporting for qualified tuition and related expenses.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Information Returns § 1.6050S-1... relating to substitute forms (see § 601.601(d)(2) of this chapter). (ii) Information included on return. An... form complies with applicable revenue procedures relating to substitute forms (see § 601.601(d)(2)...

  19. 26 CFR 1.6050S-1 - Information reporting for qualified tuition and related expenses.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Information Returns § 1.6050S-1... relating to substitute forms (see § 601.601(d)(2) of this chapter). (ii) Information included on return. An... form complies with applicable revenue procedures relating to substitute forms (see § 601.601(d)(2)...

  20. Pyruvate Kinase M2 Activates mTORC1 by Phosphorylating AKT1S1.

    PubMed

    He, Chang-Liang; Bian, Yang-Yang; Xue, Yu; Liu, Ze-Xian; Zhou, Kai-Qiang; Yao, Cui-Fang; Lin, Yan; Zou, Han-Fa; Luo, Fang-Xiu; Qu, Yuan-Yuan; Zhao, Jian-Yuan; Ye, Ming-Liang; Zhao, Shi-Min; Xu, Wei

    2016-01-01

    In cancer cells, the mammalian target of rapamycin complex 1 (mTORC1) that requires hormonal and nutrient signals for its activation, is constitutively activated. We found that overexpression of pyruvate kinase M2 (PKM2) activates mTORC1 signaling through phosphorylating mTORC1 inhibitor AKT1 substrate 1 (AKT1S1). An unbiased quantitative phosphoproteomic survey identified 974 PKM2 substrates, including serine202 and serine203 (S202/203) of AKT1S1, in the proteome of renal cell carcinoma (RCC). Phosphorylation of S202/203 of AKT1S1 by PKM2 released AKT1S1 from raptor and facilitated its binding to 14-3-3, resulted in hormonal- and nutrient-signals independent activation of mTORC1 signaling and led accelerated oncogenic growth and autophagy inhibition in cancer cells. Decreasing S202/203 phosphorylation by TEPP-46 treatment reversed these effects. In RCCs and breast cancers, PKM2 overexpression was correlated with elevated S202/203 phosphorylation, activated mTORC1 and inhibited autophagy. Our results provided the first phosphorylome of PKM2 and revealed a constitutive mTORC1 activating mechanism in cancer cells. PMID:26876154

  1. Pyruvate Kinase M2 Activates mTORC1 by Phosphorylating AKT1S1

    PubMed Central

    He, Chang-Liang; Bian, Yang-Yang; Xue, Yu; Liu, Ze-Xian; Zhou, Kai-Qiang; Yao, Cui-Fang; Lin, Yan; Zou, Han-Fa; Luo, Fang-Xiu; Qu, Yuan-Yuan; Zhao, Jian-Yuan; Ye, Ming-Liang; Zhao, Shi-Min; Xu, Wei

    2016-01-01

    In cancer cells, the mammalian target of rapamycin complex 1 (mTORC1) that requires hormonal and nutrient signals for its activation, is constitutively activated. We found that overexpression of pyruvate kinase M2 (PKM2) activates mTORC1 signaling through phosphorylating mTORC1 inhibitor AKT1 substrate 1 (AKT1S1). An unbiased quantitative phosphoproteomic survey identified 974 PKM2 substrates, including serine202 and serine203 (S202/203) of AKT1S1, in the proteome of renal cell carcinoma (RCC). Phosphorylation of S202/203 of AKT1S1 by PKM2 released AKT1S1 from raptor and facilitated its binding to 14-3-3, resulted in hormonal- and nutrient-signals independent activation of mTORC1 signaling and led accelerated oncogenic growth and autophagy inhibition in cancer cells. Decreasing S202/203 phosphorylation by TEPP-46 treatment reversed these effects. In RCCs and breast cancers, PKM2 overexpression was correlated with elevated S202/203 phosphorylation, activated mTORC1 and inhibited autophagy. Our results provided the first phosphorylome of PKM2 and revealed a constitutive mTORC1 activating mechanism in cancer cells. PMID:26876154

  2. Study of the Vibrational Spectra of the Mixed Crystal ZnS1-xSex

    NASA Astrophysics Data System (ADS)

    Basak, Tista; Rao, Mala N.; Chaplot, S. L.

    2011-07-01

    A simple transferable potential model has been employed to study the vibrational mode behavior of the mixed system ZnS1-xSex as a function of concentration and pressure. Further, the existence of a localized resonance mode has also been confirmed, in agreement with experimental data from Raman scattering.

  3. B cell-specific S1PR1 deficiency blocks prion dissemination between secondary lymphoid organs.

    PubMed

    Mok, Simon W F; Proia, Richard L; Brinkmann, Volker; Mabbott, Neil A

    2012-05-15

    Many prion diseases are peripherally acquired (e.g., orally or via lesions to skin or mucous membranes). After peripheral exposure, prions replicate first upon follicular dendritic cells (FDC) in the draining lymphoid tissue before infecting the brain. However, after replication upon FDC within the draining lymphoid tissue, prions are subsequently propagated to most nondraining secondary lymphoid organs (SLO), including the spleen, by a previously underdetermined mechanism. The germinal centers in which FDC are situated produce a population of B cells that can recirculate between SLO. Therefore, we reasoned that B cells were ideal candidates by which prion dissemination between SLO may occur. Sphingosine 1-phosphate receptor (S1PR)1 stimulation controls the egress of T and B cells from SLO. S1PR1 signaling blockade sequesters lymphocytes within SLO, resulting in lymphopenia in the blood and lymph. We show that, in mice treated with the S1PR modulator FTY720 or with S1PR1 deficiency restricted to B cells, the dissemination of prions from the draining lymph node to nondraining SLO is blocked. These data suggest that B cells interacting with and acquiring surface proteins from FDC and recirculating between SLO via the blood and lymph mediate the initial propagation of prions from the draining lymphoid tissue to peripheral tissues. PMID:22504650

  4. Crystallization and preliminary crystallographic study of the yeast Malassezia sympodialis allergen Mala s 1

    SciTech Connect

    Vilhelmsson, Monica; Hallberg, B. Martin; Rasool, Omid; Zargari, Arezou; Scheynius, Annika; Achour, Adnane

    2006-02-01

    Crystals of the M. sympodialis allergen Mala s 1 have been obtained using the hanging-drop vapour-diffusion method. A diffraction data set has been collected from native crystals to 1.35 Å resolution. The opportunistic yeast Malassezia sympodialis can act as an allergen and elicit specific IgE- and T-cell reactivity in patients with atopic eczema. The first identified major allergen from M. sympodialis, Mala s 1, is present on the cell surface of the yeast. Recombinant Mala s 1 was expressed in Escherichia coli, purified and refolded in a soluble form. Crystals of Mala s 1 were obtained in 25% PEG 8K, 0.2 M (NH{sub 4}){sub 2}SO{sub 4}. Crystals belong to space group P2{sub 1}2{sub 1}2, with unit-cell parameters a = 44.4, b = 163.7, c = 50.6 Å, and diffract to 1.35 Å resolution.

  5. Determination of the hyperfine coupling constant of the cesium 7S1/2 state

    NASA Astrophysics Data System (ADS)

    Yang, Guang; Wang, Jie; Yang, Baodong; Wang, Junmin

    2016-08-01

    We report the hyperfine splitting (HFS) measurement of the cesium (Cs) 7S1/2 state by optical–optical double-resonance spectroscopy with the Cs 6S1/2–6P3/2–7S1/2 (852 nm  +  1470 nm) ladder-type system. The HFS frequency calibration is performed by employing a phase-type waveguide electro-optic modulator together with a stable confocal Fabry–Perot cavity. From the measured HFS between the F″  =  3 and F″  =  4 manifolds of the Cs 7S1/2 state (HFS  =  2183.273  ±  0.062 MHz), we have determined the magnetic dipole hyperfine coupling constant (A  =  545.818  ±  0.016 MHz), which is in good agreement with the previous work but much more precise.

  6. Creation of a S1P Lyase bacterial surrogate for structure-based drug design.

    PubMed

    Argiriadi, Maria A; Banach, David; Radziejewska, Elzbieta; Marchie, Susan; DiMauro, Jennifer; Dinges, Jurgen; Dominguez, Eric; Hutchins, Charles; Judge, Russell A; Queeney, Kara; Wallace, Grier; Harris, Christopher M

    2016-05-01

    S1P Lyase (SPL) has been described as a drug target in the treatment of autoimmune diseases. It plays an important role in maintaining intracellular levels of S1P thereby affecting T cell egress from lymphoid tissues. Several groups have already published approaches to inhibit S1P Lyase with small molecules, which in turn increase endogenous S1P concentrations resulting in immunosuppression. The use of structural biology has previously aided SPL inhibitor design. Novel construct design is at times necessary to provide a reagent for protein crystallography. Here we present a chimeric bacterial protein scaffold used for protein X-ray structures in the presence of early small molecule inhibitors. Mutations were introduced to the bacterial SPL from Symbiobacterium thermophilum which mimic the human enzyme. As a result, two mutant StSPL crystal structures resolved to 2.8Å and 2.2Å resolutions were solved and provide initial structural hypotheses for an isoxazole chemical series, whose optimization is discussed in the accompanying paper. PMID:27013389

  7. Dramatic Response of S-1 Administration to Chemorefractory Advanced Thymic Cancer.

    PubMed

    Kaira, Kyoichi; Naruse, Ichiro; Imai, Hisao; Sunaga, Noriaki; Hisada, Takeshi; Motegi, Masahiko; Asao, Takayuki; Yamada, Masanobu

    2014-01-01

    Thymic cancer (TC) is a rare malignancy in thoracic tumors, and there has been no standard therapeutics for advanced or relapsed patients. The clinical significance of second-line or beyond chemotherapy for platinum refractory advanced TC remains unclear. Here, we present the experience of a patient with TC showing a complete response to S-1 as third-line chemotherapy. A 54-year-old female with TC was treated with carboplatin plus paclitaxel and thoracic radiotherapy as first-line chemoradiotherapy and amrubicin as second-line chemotherapy. After 3 cycles of amrubicin administration, the metastatic hepatic lesions revealed a markedly progressive disease. A single agent of S-1 was administered as sequencing chemotherapy. After 2 cycles of S-1, the patient achieved a complete remission of multiple metastatic sites. There was evidence of immunohistochemical staining of a low thymidylate synthase (TS) expression. The expression of TS may be closely associated with the efficacy of S-1 in patients with TC. PMID:26389778

  8. Spin-dependent, optogalvanic effects of laser-pumped He(2/3/S1) atoms

    NASA Astrophysics Data System (ADS)

    Schearer, L. D.; Tin, Pedetha

    1989-10-01

    Spin-dependent optogalvanic effects of laser-pumped He(2/3/S1) atoms are demonstrated. As helium atoms are excited with an IR tunable laser, changes in the conductivity of helium radio-frequency discharge are observed. With approximately 1 mW/sq cm of tunable laser power near 1.083 microns, the intensity-modulated optogalvanic effect signals are obtained as the laser is tuned through the D0(2/3/S1-2/3/P0), D1(2/3/S1-2/3/P1), and D2(2/3/S1-2/3/P2) transitions at 1.082908, 1.083025, and 1.083034 microns, respectively. If the laser emission is now circularly polarized and directed onto the helium discharge cell with the applied field parallel to the pump axis, some of the metastable atoms are oriented with their electronic spins along the field direction, modulating the coil current. One of the important applications of spin-polarized ensembles of metastable 4He is in extremely sensitive magnetic-field measuring devices.

  9. Structure of the S1S2 Glutamate Binding Domain of GluR3

    PubMed Central

    Ahmed, Ahmed H.; Wang, Qi; Sondermann, Holger; Oswald, Robert E.

    2009-01-01

    Glutamate receptors are the most prevalent excitatory neurotransmitter receptors in the vertebrate central nervous system. Determining the structural differences between the binding sites of different subtypes is crucial to our understanding of neuronal circuits and to the development of subtype specific drugs. The structures of the binding domain (S1S2) of the GluR3 (flip) AMPA receptor subunit bound to glutamate and AMPA and the GluR2 (flop) subunit bound to glutamate were determined by X-ray crystallography to 1.9, 2.1, and 1.55 Å, respectively. Overall, the structure of GluR3 (flip) S1S2 is very similar to GluR2 (flop) S1S2 (backbone RMSD of 0.30 ± 0.05 for glutamate-bound and 0.26 ± 0.01 for AMPA-bound). The differences in the flip and flop isoforms are subtle and largely arise from one hydrogen bond across the dimer interface and associated water molecules. Comparison of the binding affinity for various agonists and partial agonists suggest that the S1S2 domains of GluR2 and GluR3 show only small differences in affinity, unlike what is found for the intact receptors (with the exception of one ligand, Cl-HIBO, which has a ten-fold difference in affinity for GluR2 vs GluR3). PMID:19003990

  10. High-Dispersion Spectroscopic Observations of Comet C/2012 S1 (ISON) with the Subaru Telescope

    NASA Astrophysics Data System (ADS)

    Shinnaka, Yoshiharu; Kawakita, Hideyo; Nagashima, Masayoshi; Hitomi, Kobayashi; Decock, Alice; Jehin, Emmanuel; Boice, Daniel C.

    2014-11-01

    Comet C/2012 S1 (ISON) was one of the Oort cloud comets and dynamically new. This comet was broken at its perihelion passage on UT 2013 November 28.1 (at Rh ~ 17 solar radius). We observed the comet C/2012 S1 (ISON) on UT 2013 November 15 with the High Dispersion Spectrograph (HDS) mounted on the Subaru Telescope atop Mauna Kea, Hawaii. Its heliocentric and geocentric distances were 0.601 and 0.898 AU, respectively. We selected the slit size of 0”.5 x 9”.0 on the sky to achieve the spectral resolution of R = 72,000 from 550 to 830 nm. The total exposure time of comet C/2012 S1 (ISON) was 1200 seconds. We detected many emission lines caused from radicals (e.g., CN, C2, NH2), ions (H2O+), atoms ([OI] and Na I) and also many unidentified lines in the spectra. We report the (1) the ortho-to-para abundance ratios (OPRs) of water and ammonia estimated from the high-dispersion spectra of H2O+ and NH2, (2) the green-to-red line ratio of forbidden oxygen emissions, (3) the isotopic ratios of C2 (the carbon isotopic ratio from Swan band) and CN (the carbon and nitrogen isotopic ratios from red band), (4) the sodium-to-continuum ratio of comet C/2012 S1 (ISON).

  11. Pan-STARRS 1 observations of the unusual active Centaur P/2011 S1(Gibbs)

    SciTech Connect

    Lin, H. W.; Ip, W. H.; Chen, W. P.; Chen, Y. T.; Lacerda, P.; Holman, M.; Protopapas, P.; Burgett, W. S.; Chambers, K. C.; Flewelling, H.; Huber, M. E.; Jedicke, R.; Kaiser, N.; Magnier, E. A.; Metcalfe, N.; Price, P. A.

    2014-05-01

    P/2011 S1 (Gibbs) is an outer solar system comet or active Centaur with a similar orbit to that of the famous 29P/Schwassmann-Wachmann 1. P/2011 S1 (Gibbs) has been observed by the Pan-STARRS 1 (PS1) sky survey from 2010 to 2012. The resulting data allow us to perform multi-color studies of the nucleus and coma of the comet. Analysis of PS1 images reveals that P/2011 S1 (Gibbs) has a small nucleus <4 km radius, with colors g {sub P1} – r {sub P1} = 0.5 ± 0.02, r {sub P1} – i {sub P1} = 0.12 ± 0.02, and i {sub P1} – z {sub P1} = 0.46 ± 0.03. The comet remained active from 2010 to 2012, with a model-dependent mass-loss rate of ∼100 kg s{sup –1}. The mass-loss rate per unit surface area of P/2011 S1 (Gibbs) is as high as that of 29P/Schwassmann-Wachmann 1, making it one of the most active Centaurs. The mass-loss rate also varies with time from ∼40 kg s{sup –1} to 150 kg s{sup –1}. Due to its rather circular orbit, we propose that P/2011 S1 (Gibbs) has 29P/Schwassmann-Wachmann 1-like outbursts that control the outgassing rate. The results indicate that it may have a similar surface composition to that of 29P/Schwassmann-Wachmann 1. Our numerical simulations show that the future orbital evolution of P/2011 S1 (Gibbs) is more similar to that of the main population of Centaurs than to that of 29P/Schwassmann-Wachmann 1. The results also demonstrate that P/2011 S1 (Gibbs) is dynamically unstable and can only remain near its current orbit for roughly a thousand years.

  12. Characterization of a periplasmic S1-like nuclease coded by the Mesorhizobium loti symbiosis island

    SciTech Connect

    Pimkin, Maxim; Miller, C. Glenn; Blakesley, Lauryn; Oleykowski, Catherine A.; Kodali, Nagendra S.; Yeung, Anthony T. . E-mail: AT_Yeung@fccc.edu

    2006-04-28

    DNA sequences encoding hypothetical proteins homologous to S1 nuclease from Aspergillus oryzae are found in many organisms including fungi, plants, pathogenic bacteria, and eukaryotic parasites. One of these is the M1 nuclease of Mesorhizobium loti which we demonstrate herein to be an enzymatically active, soluble, and stable S1 homolog that lacks the extensive mannosyl-glycosylation found in eukaryotic S1 nuclease homologs. We have expressed the cloned M1 protein in M. loti and purified recombinant native M1 to near homogeneity and have also isolated a homogeneous M1 carboxy-terminal hexahistidine tag fusion protein. Mass spectrometry and N-terminal Edman degradation sequencing confirmed the protein identity. The enzymatic properties of the purified M1 nuclease are similar to those of S1. At acidic pH M1 is 25 times more active on single-stranded DNA than on double-stranded DNA and 3 times more active on single-stranded DNA than on single-stranded RNA. At neutral pH the RNase activity of M1 exceeds the DNase activity. M1 nicks supercoiled RF-I plasmid DNA and rapidly cuts the phosphodiester bond across from the nick in the resultant relaxed RF-II plasmid DNA. Therefore, M1 represents an active bacterial S1 homolog in spite of great sequence divergence. The biochemical characterization of M1 nuclease supports our sequence alignment that reveals the minimal 21 amino acid residues that are necessarily conserved for the structure and functions of this enzyme family. The ability of M1 to degrade RNA at neutral pH implies previously unappreciated roles of these nucleases in biological systems.

  13. The S1 Truss Prior to Installation on the International Space Station

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Being attached to the Canadarm2 on the International Space Station (ISS), the Remote Manipulator System arm built by the Canadian Space Agency, the Integrated Truss Assembly (S1) Truss is suspended over the Space Shuttle Orbiter Atlantis' cargo bay. Astronauts Sandra H. Magnus, STS-112 mission specialist, and Peggy A. Whitson, Expedition Five flight engineer, used the Canadarm2 from inside the Destiny laboratory on the ISS to lift the S1 truss out of the orbiter's cargo bay and move it into position prior to its installation on the ISS. The primary payloads of this mission, ISS Assembly Mission 9A, were the Integrated Truss Assembly S1 (S One), the starboard side thermal radiator truss, and the Crew Equipment Translation Aid (CETA) cart to the ISS. The S1 truss provides structural support for the orbiting research facility's radiator panels, which use ammonia to cool the Station's complex power system. The S1 truss was attached to the S0 (S Zero) truss, which was launched on April 8, 2002 aboard the STS-110, and flows 637 pounds of anhydrous ammonia through three heat-rejection radiators. The truss is 45-feet long, 15-feet wide, 10-feet tall, and weighs approximately 32,000 pounds. The CETA cart was attached to the Mobil Transporter and will be used by assembly crews on later missions. Manufactured by the Boeing Company in Huntington Beach, California, the truss primary structure was transferred to the Marshall Space Flight Center in February 1999 for hardware installations and manufacturing acceptance testing. The launch of the STS-112 mission occurred on October 7, 2002, and its 11-day mission ended on October 18, 2002.

  14. Centennial-scale paleoceanography during sapropel S1 deposition in the NE Aegean (Mediterranean Sea)

    NASA Astrophysics Data System (ADS)

    Triantaphyllou, Maria; Gogou, Alexandra; Dimiza, Margarita; Kostopoulou, Sofia; Parinos, Constantine; Roussakis, Grigoris; Geraga, Maria; Skampa, Elisavet; Bouloubassi, Ioanna; Fleitmann, Dominik; Zervakis, Vassilis; Velaoras, Dimitris; Diamantopoulou, Antonia; Sampatakaki, Angeliki; Lykousis, Vassilis

    2016-04-01

    Combined micropaleontological and geochemical analyses in the high-sedimentation gravity core M-4G, provided new centennial scale paleoceanographic data for the sapropel S1 deposition in the NE Aegean Sea. Sapropel layer S1a (10.2-8.0 ka) is deposited in dysoxic to oxic bottom waters; sediments are characterized by the high abundance of benthic foraminifers Chilostomella mediterranensis and Globobulimina affinis that are able to tolerate surface sediment and/or pore water oxygen depletion and the presence of the oxic mesotrophic-eutrophic U. mediterranea. Adequate preservation of organic matter is proven by the high organic carbon and loliolide and isololiolide contents, whereas the biomarker record and the abundances of eutrophic planktonic foraminifera document enhanced productivity. Both alkenone-based SSTs and δO18 G. bulloides records indicate coolings at 8.2 ka (S1a) and at ~7.8 ka (S1 interruption). Sapropelic layer S1b (7.7-6.4 ka) is characterized by rather oxic conditions marked by the prominent increase of U. mediterranea. The highly fluctuating SSTs demonstrate repeated coolings and associated dense water formation; major event at 7.4 ka, followed by cold spells at 7.0, 6.8, 6.5 ka. Besides, the increase of algal biomarkers, labile organic matter-feeding foraminifera and eutrophic planktonic species pinpoints rise in in situ marine productivity, which is enhanced by more efficient vertical convection due to repeated cold events. The associated contributions of labile marine organic matter (OM) along with fresher terrestrial OM inputs after ~7.7 ka BP imply alternative/ additional than the north Aegean riverine borderland sources for the influx of organic matter at the south Limnos Basin, also related to the inflow of highly productive Marmara/Black Sea waters

  15. Sphingosine 1-phosphate analogue recognition and selectivity at S1P4 within the endothelial differentiation gene family of receptors

    PubMed Central

    Inagaki, Yuichi; Pham, TrucChi T.; Fujiwara, Yuko; Kohno, Takayuki; Osborne, Daniel A.; Igarashi, Yasuyuki; Tigyi, Gabor; Parrill, Abby L.

    2005-01-01

    Synergistic computational and experimental studies provided previously unforeseen details concerning the structural basis of S1P (sphingosine 1-phosphate) recognition by the S1P4 G-protein-coupled receptor. Similarly to reports on the S1P1 receptor, cationic and anionic residues in the third transmembrane domain (R3.28 and E3.29 at positions 124 and 125) form ion pairs with the phosphate and ammonium of S1P, and alanine mutations at these positions abolished specific S1P binding, S1P-induced receptor activation and cell migration. Unlike findings on the S1P1 receptor, no cationic residue in the seventh transmembrane domain interacts with the phosphate. Additionally, two previously undiscovered interactions with the S1P polar headgroup have been identified. Trp186 at position 4.64 in the fourth transmembrane domain interacts by a cation-π interaction with the ammonium group of S1P. Lys204 at position 5.38 forms an ion pair with the S1P. The S1P4 and S1P1 receptors show differences in binding-pocket shape and electrostatic distributions that correlate with the published structure–activity relationships. In particular, the binding pocket of mS1P4 (mouse S1P4) has recognition sites for the anionic phosphate and cationic ammonium groups that are equidistant from the end of the non-polar tail. In contrast, the binding pocket of hS1P1 (human S1P4) places the ammonium recognition site 2 Å (1 Å=0.1 nm) closer to the end of the non-polar tail than the phosphate recognition site. PMID:15733055

  16. Enhanced regeneration of phosphorus during formation of the most recent eastern Mediterranean sapropel (S1)

    NASA Astrophysics Data System (ADS)

    Slomp, Caroline P.; Thomson, John; de Lange, Gert J.

    2002-04-01

    Phosphorus regeneration and burial fluxes during and after formation of the most recent sapropel S1 were determined for two deep-basin, low-sedimentation sites in the eastern Mediterranean Sea. Organic C/P ratios and burial fluxes indicate enhanced regeneration of P relative to C during deposition of sapropel S1. This is largely due to the enhanced release of P from organic matter during sulfate reduction. Release of P from Fe-bound P also increased, but this was only a relatively minor source of dissolved P. Pore-water HPO 42- concentrations remained too low for carbonate fluorapatite formation. An increased burial of biogenic Ca-P (i.e., fish debris) was observed for one site. Estimated benthic fluxes of P during sapropel formation were elevated relative to the present day (˜900 to 2800 vs. ˜70 to 120 μmol m -2 yr -1). The present-day sedimentary P cycle in the deep-basin sediments is characterized by two major zones of reaction: (1) the zone near the sediment-water interface where substantial release of HPO 42- from organic matter takes place, and (2) the oxidation front at the top of the S1 where upward-diffusing HPO 42- from below the sapropel is sorbed to Fe-oxides. The efficiency of aerobic organisms in retaining P is reflected in the low organic C/P ratios in the oxidized part of the sapropel. Burial efficiencies for reactive P were significantly lower during S1 times compared with the present day (˜7 to 15% vs. 64 to 77%). Budget calculations for the eastern Mediterranean Sea demonstrate that the weakening of the antiestuarine circulation and the enhanced regeneration of P both contributed to a significant increase in deep-water HPO 42- concentrations during sapropel S1 times. Provided that sufficient vertical mixing occurred, enhanced regeneration of P at the seafloor may have played a key role in maintaining increased productivity during sapropel S1 formation.

  17. The Character of the Long-Lived State Formed from S_1 of Phenylacetylene

    NASA Astrophysics Data System (ADS)

    Johnson, Philip M.; Sears, Trevor J.

    2013-06-01

    Compared to other small aromatic molecules, phenylacetylene (PA) and benzonitrile exhibit strikingly anomalous photophysics on excitation to the S_1 state. Firstly, products are formed on S_1 excitation of a beam-cooled sample that seem to live indefinitely (as defined by the flight time through the apparatus), while action spectra of their formation mirror the rotationally-resolved absorption spectrum of the monomer. Secondly, the long lived products appear immediately during the nsec. laser pulse rather than build up during the lifetime of the singlet level, as is seen in benzene, for example. The question has therefore arisen: is the long lived product of the S_1 excitation the triplet state, as is assumed in all previous work on other molecules, or is it an isomer of some sort? New pump-probe ionization mass spectroscopy experiments have been performed to study the distribution of fragments and metastable ions produced by PA cation derived from the neutral S_1 state, and from the long-lived species. These combined with other experimental results showing weak long-lived components in both the S_1 fluorescence and pump-probe photoelectron spectra that we interpret as recurrence behavior, definitively show the long-lived state is a triplet state of PA, not an isomer. PA with a singlet-triplet gap of 10000 cm^{-1} is acting like intermediate case molecules with much smaller singlet-triplet gaps such as pyrazine and pyrimidine. Calculations point to the existence of four triplet states of PA at or below the energy of S_1 providing a very large density of vibronic states in which to distribute the energy from singlet-triplet crossing. PA T_1 is calculated to be non-planar, in contrast to what is found in benzene, possibly helping to explain the different photophysics. Acknowledgments: We gratefully acknowledge G. V. Lopez for his contributions to some of the experimental masurements. Work at Brookhaven National Laboratory was carried out under Contract No. DE-AC02

  18. Raman spectrum of bacteriochlorophyll a in the S1 state

    NASA Astrophysics Data System (ADS)

    Nishizawa, Ei-ichi; Hashimoto, Hideki; Koyama, Yasushi

    1991-07-01

    The S 1 Raman spectrum of bacteriochlorophyll a is reported for the first time. A one-color experiment using the 351 nm picosecond pulses (duration 50 ps and repetition 1 kHz) for tetrahydrofuran solution detected a transient species, which showed distinct Raman lines at 1567, 1409 and 1320 cm -1 and weak profiles around 1169, 1092, 1051 and 794 cm -1. The other one-color experiment using the 355 nm nanosecond pulses (duration 12 ns and repetition 10 Hz) detected the T 1 species reported previously showing Raman lines at 1578 and 1330 cm -1. Thus, the newly identified transient species, which was pumped and probed within 50 ps, is assigned to S 1.

  19. Photoionization of DABCO via high vibrational levels of the S 1 state

    NASA Astrophysics Data System (ADS)

    Pratt, S. T.

    2002-07-01

    The photoelectron spectrum following resonant two-photon ionization of 1,4-diazabicyclo[2.2.2]octane (DABCO) was recorded with the laser tuned to the origin band of the S 2←S 0 transition. The spectrum is consistent with the rapid radiationless transition from the S 2 state into high vibrational levels of the S 1 state, as proposed by Smith et al. [J. Phys. Chem. 88 (1984) 2250]. Features in the double-resonance spectrum of Smith et al. that were previously assigned to photoionization of S(-) 3s(-) 1A″2 vibrational levels populated by a radiationless transition from the S 2 state are reinterpreted, with the conclusion that the S(-) state has yet to be observed.

  20. S1 and S2 Excited States of Gas-Phase Schiff-Base Retinal Chromophores

    NASA Astrophysics Data System (ADS)

    Nielsen, I. B.; Lammich, L.; Andersen, L. H.

    2006-01-01

    Photoabsorption studies of 11-cis and all-trans Schiff-base retinal chromophore cations in the gas phase have been performed at the electrostatic ion storage ring in Aarhus. A broad absorption band due to the optically allowed excitation to the first electronically excited singlet state (S1) is observed at around 600 nm. A second “dark” excited state (S2) just below 400 nm is reported for the first time. It is located ˜1.2eV above S1 for both chromophores. The S2 state was not visible in a solution measurement where only one highly blueshifted absorption band corresponding to the first excited state was visible. Knowledge of the position of the excited states in retinal is essential for the understanding of the fast photoisomerization in, for example, visual pigments.

  1. L4-L5-S1 human dermatomes: a clinical, electromyographical, imaging and surgical findings.

    PubMed

    Faleiros, Antonio Tadeu de Souza; Resende, Luiz Antonio de Lima; Zanini, Marco Antonio; Castro, Heloisa Amélia de Lima; Gabarra, Roberto Colichio

    2009-06-01

    There is substantial controversy in literature about human dermatomes. We studied L4, L5, and S1 inferior limb dermatomes by comparing clinical signs and symptoms with conduction studies, electromyographical data, neurosurgical findings, and imaging data from computerized tomography (CT) or magnetic resonance imaging (MRI). After analyzing 60 patients, we concluded that L4 is probably located in the medial aspect of the leg, L5 in the lateral aspect of the leg and foot dorsus, and S1 in the posterior aspect of the backside, tight, leg and plantar foot skin. This is the first time that these human dermatomes have been evaluated by combined analysis of clinical, electromyographical, neurosurgical, and imaging data. PMID:19547820

  2. Atheroprotective role of high-density lipoprotein (HDL)-associated sphingosine-1-phosphate (S1P).

    PubMed

    Potì, Francesco; Simoni, Manuela; Nofer, Jerzy-Roch

    2014-08-01

    Numerous epidemiological studies documented an inverse relationship between plasma high-density lipoprotein (HDL) cholesterol levels and the extent of atherosclerotic disease. However, clinical interventions targeting HDL cholesterol failed to show clinical benefits with respect to cardiovascular risk reduction, suggesting that HDL components distinct from cholesterol may account for anti-atherogenic effects attributed to this lipoprotein. Sphingosine-1-phosphate (S1P)-a lysosphingolipid exerting its biological activity via binding to specific G protein-coupled receptors and regulating a wide array of biological responses in a variety of different organs and tissues including the cardiovascular system-has been identified as an integral constituent of HDL particles. In the present review, we discuss current evidence from epidemiological studies, experimental approaches in vitro, and animal models of atherosclerosis, suggesting that S1P contributes to atheroprotective effects exerted by HDL particles. PMID:24891400

  3. Effects of mutations on enzyme activity and immunoreactivity of the S1 subunit of pertussis toxin.

    PubMed Central

    Lobet, Y; Cieplak, W; Smith, S G; Keith, J M

    1989-01-01

    By introducing a series of six different substitutions at and around position 9, we investigated the structural requirements of the amino-terminal region of the S1 subunit of pertussis toxin for both enzyme activity and immunoreactivity. All mutant S1 analogs with a substitution at this location exhibited severely decreased ADP-ribosyltransferase activity (range, 400- to 2,500-fold). In contrast, alteration of arginine 58 had considerably less effect. The reactivity of the mutant molecules with monoclonal antibody 1B7 varied with the nature of the substitution. These findings indicate an absolute requirement for the presence of an arginine residue at position 9 for the maintenance of efficient ADP-ribosyltransferase activity and illustrate the specific participation of vicinal residues in the formation of the protective epitope. PMID:2807541

  4. [Complete response in a case of anastomotic recurrence of rectal cancer treated with S-1 monotherapy].

    PubMed

    Kabashima, Akira; Kitagawa, Dai; Nakamura, Toshihiko; Kondo, Naoko; Teramoto, Seiichi; Saito, Genkichi; Funahashi, Tomoru; Adachi, Eisuke; Ikeda, Yoichi

    2014-11-01

    A 63-year-old woman underwent a low anterior resection for rectal cancer in 2002.A n anastomotic recurrence was diagnosed in July 2011.S he rejected the possibility of colostomy as radical surgery.Chemotherapy consisting of capecitabine+ oxaliplatin (XELOX) or folinic acid, fluorouracil, and oxaliplatin (FOLFOX6) + bevacizumab were not possible because of high costs. In view of the lower costs and the potential for ambulation, S-1 monotherapy was started. After 3 months, a reduction in the recurrent lesion was observed.After 19 months, the recurrent lesion revealed a scar, which was judged by biopsy to be Group 1.We had achieved a pathological complete response (CR).The standard treatment for recurrent colon cancer is surgical resection or multidrug chemotherapy. However, in view of a patient's quality of life (QOL), S-1 monotherapy may be considered as a potential therapy. PMID:25731306

  5. [R0 Resection of Locally Advanced Pancreatic Cancer after Combination Chemotherapy with Gemcitabine and S-1].

    PubMed

    Kametaka, Hisashi; Makino, Hironobu; Fukada, Tadaomi; Seike, Kazuhiro; Koyama, Takashi; Hasegawa, Akio

    2015-11-01

    A 68-year-old female was referred to our institution in October 2014 for additional therapy for cancer of the head of the pancreas. Utilizing a computed tomography scan, he was initially diagnosed with locally advanced unresectable cancer because of massive invasion to the superior mesenteric artery (SMA). Combination chemotherapy consisting of gemcitabine and S-1 was administrated for 10 months. Since the tumor was remarkably reduced after chemotherapy, pancreaticoduodenectomy combined with portal vein resection was performed. Since the histopathological findings indicated few residual cancer tissues, our chemotherapy was considered dramatically effective. The postoperative course was uneventful and the patient remains well and without any recurrences 14 months after the surgery. We therefore report a case of locally unresectable pancreatic cancer, which achieved R0 resection after combination chemotherapy with gemcitabine and S-1. PMID:26805123

  6. Structure and tensile strength of LaS(1.4)

    NASA Technical Reports Server (NTRS)

    Whittenberger, J. Daniel; Smoak, Richard H.

    1987-01-01

    The tensile strength of LaS(1.4) has been estimated by diametral stress testing at room temperature, 800 and 1300 K. Brittle, tensile-type failures were obtained at all temperatures when the crosshead speed was 0.0021 mm/s; however, a 1300 K test at 0.00085 mm/s produced plastic flow. The microstructure of LaS(1.4) consisted of two phases with beta-La2S3 comprising about 15 vol percent of the structure and gamma-La2S3 the remainder. Because of the limited amount of material available for testing, no correlation between microstructure and mechanical strength could be drawn.

  7. Reduced dimension rovibrational variational calculations of the S(1) state of C2H2. II. The S(1) rovibrational manifold and the effects of isomerization.

    PubMed

    Changala, P Bryan; Baraban, Joshua H; Stanton, John F; Merer, Anthony J; Field, Robert W

    2014-01-14

    Reduced dimension variational calculations have been performed for the rovibrational level structure of the S1 state of acetylene. The state exhibits an unusually complicated level structure, for various reasons. First, the potential energy surface has two accessible conformers, trans and cis. The cis conformer lies about 2700 cm(-1) above the trans, and the barrier to cis-trans isomerization lies about 5000 cm(-1) above the trans minimum. The trans vibrations ν4 (torsion) and ν6 (asym. bend) interact very strongly by Darling-Dennison and Coriolis resonances, such that their combination levels and overtones form polyads with unexpected structures. Both conformers exhibit very large x36 cross-anharmonicity since the pathway to isomerization is a combination of ν6 and ν3 (sym. bend). Near the isomerization barrier, the vibrational levels show an even-odd K-staggering of their rotational levels as a result of quantum mechanical tunneling through the barrier. The present calculations address all of these complications, and reproduce the observed K-structures of the bending and C-C stretching levels with good qualitative accuracy. It is expected that they will assist with the assignment of the irregular patterns near the isomerization barrier. PMID:24437883

  8. Diboson Production Cross Sections at $\\sqrt{s}=1.96$ TeV

    SciTech Connect

    Sekaric, Jadranka

    2009-05-01

    The increasing size of the data recorded by the CDF and D0 experiments at the Tevatron collider at {radical}s = 1.96 TeV makes the diboson physics program more accessible for probes of the electroweak gauge structure in the Standard Model. Here we summarize the most recent measurements of the diboson cross sections and limits on the trilinear gauge boson couplings.

  9. Infrared reflectivity spectra of GaS 1-xSe x mixed crystals

    NASA Astrophysics Data System (ADS)

    Riede, V.; Neumann, H.; Sobotta, H.; Lévy, F.

    1980-04-01

    Infrared reflectivity spectra of GaS 1- xSe x mixed crystals are measured for E ‖ c in the wavenumber range from 180 to 4000 cm -1. Two-mode behaviour is found for the infrared active optical modes. The composition dependence of the mode frequencies can be described by the MREI model if a nonlinear change of the force constants with composition is assumed.

  10. Dihydroartemisinin restricts hepatic stellate cell contraction via an FXR-S1PR2-dependent mechanism.

    PubMed

    Xu, Wenxuan; Lu, Chunfeng; Zhang, Feng; Shao, Jiangjuan; Zheng, Shizhong

    2016-05-01

    Hepatic stellate cells (HSCs) are universally acknowledged to play a stimulative role in the pathogenesis of hepatic fibrosis and portal hypertension. HSCs when activated in response to liver injury are characterized with many changes, with HSC contraction being the most common cause of portal hypertension. Previous studies have shown that dihydroartemisinine (DHA) is a potential antifibrotic natural product by inducing HSC apoptosis, whereas the role of DHA in regulating HSC contraction and the mechanisms involved remain a riddle. Recent studies have emphasized on the importance of farnesoid X receptor (FXR) and sphingosine-1-phosphate receptor 2 (S1PR2) in controlling cell contractility. This study showed that DHA strongly induced the mRNA and protein expression of FXR in LX-2 cells in a dose- and time-dependent manner and inhibited HSC activation, implying a conceivable impact of DHA on HSC contraction. The gel contraction assays and fluorescence staining of actin cytoskeleton verified that DHA dose-dependently limited contraction of collagen lattices and reorganization of actin stress fibers in LX-2 cells. DHA also decreased the phosphorylation of myosin light chain that is responsible for the contractile force of HSCs. Furthermore, gain- or loss-of-function analyses exhibited a FXR- and S1PR2-dependent mechanism of inhibiting HSC contraction by DHA, and DHA decreased S1PR2 expression by modulating FXR activation. Subsequent work revealed that inhibition of both Ca(2+) -dependent and Ca(2+) -sensitization signaling transductions contributed to DHA-induced HSC relaxation. In summary, these findings suggest that DHA could restrict HSC contraction through modulating FXR/S1PR2 pathway-mediated Ca(2+) -dependent and Ca(2+) -sensitization signaling. Our discoveries make DHA a potential candidate for portal hypertension. © 2016 IUBMB Life 68(5):376-387, 2016. PMID:27027402

  11. Regarding the Charmed-Strange Member of the 23S1 Meson State

    PubMed Central

    Feng, Xue-Chao; Chen, Jing

    2013-01-01

    By employing the mass relations derived from the mass matrix and Regge trajectory, we investigate the masses of charmed and charmed-strange members of the 23S1 meson. The masses are compared with the values predicted by other theoretical approaches and experimental data. The results may be useful for the discovery of the unobserved meson and the determination of the quantum number of the newly discovered states. PMID:24250272

  12. Multiple activities of RNA-binding proteins S1 and Hfq.

    PubMed

    Hajnsdorf, Eliane; Boni, Irina V

    2012-07-01

    In all organisms, RNA-binding proteins participate in modulating all the steps in the life cycle of RNA, including transcription, folding, translation and turnover. In bacteria, RNA-binding proteins may be specific for a few RNA targets (e.g., several ribosomal proteins that recognize both rRNA during ribosome assembly and their own mRNAs when acting as highly specific autogenous repressors) or function as global regulators implicated in numerous regulatory networks. Some RNA-binding proteins combine all these features, and this particularly concerns the ribosomal protein S1 and the Sm-like protein Hfq. S1 is a key mRNA-binding protein in gram-negative bacteria; it recognizes mRNA leaders and provides binding of diverse mRNAs to the ribosome at the initiation step of translation. Moreover, S1 is a highly specific autogenous repressor that is able to distinguish its own mRNA from all the others. Hfq is recognized as a global regulator that facilitates small RNA-mRNA interactions in bacteria; it thereby controls the expression of many mRNAs either positively or negatively. In addition, these two proteins were reported to affect transcription, RNA degradation and other processes. Although they have no sequence specificity, Hfq and S1 preferentially bind A/U-rich single-stranded RNA regions; despite this, they nevertheless carry out very different tasks in the cell. This review is focused on the diversity of functions that can be performed by these abundant RNA-binding bacterial proteins. PMID:22370051

  13. [A case of sigmoid colon cancer with multiple liver metastases responding to S-1].

    PubMed

    Maruyama, Tsunehiko; Takagaki, Toshiro; Hara, Ken; Ohkohchi, Nobuhiro

    2008-02-01

    A 74-year-old woman was referred to our hospital with complaints of constipation and abdominal distention caused by a sigmoid colon tumor. After examination, she was diagnosed as sigmoid colon cancer with multiple liver metastases. To prevent bowel obstruction, a sigmoid colon resection was performed. On postoperative days 15, S-1 was started, and she was discharged on postoperative day 26. Each course consisted of daily oral administration S-1 for 4 weeks followed by 2 drug-free weeks. However, because of grade 2 anorexia in the 1st course, the treatment plan was changed to administration for 2 weeks and withdrawal for 1 week. After 7 courses of treatment, computed tomography revealed that the liver metastases were remarkably reduced. Although she experienced an adverse event involving a cutaneous symptom of grade 2, the treatment was continued under ambulatory management. After eight courses, elevation of tumor marker and metastasis at the right femur were found, and she died of the cancer 12 months after the operation. S-1 is expected to be an effective agent for the treatment of advanced colorectal cancer. PMID:18281773

  14. Short Time-Scale Sensory Coding in S1 during Discrimination of Whisker Vibrotactile Sequences.

    PubMed

    McGuire, Leah M; Telian, Gregory; Laboy-Juárez, Keven J; Miyashita, Toshio; Lee, Daniel J; Smith, Katherine A; Feldman, Daniel E

    2016-08-01

    Rodent whisker input consists of dense microvibration sequences that are often temporally integrated for perceptual discrimination. Whether primary somatosensory cortex (S1) participates in temporal integration is unknown. We trained rats to discriminate whisker impulse sequences that varied in single-impulse kinematics (5-20-ms time scale) and mean speed (150-ms time scale). Rats appeared to use the integrated feature, mean speed, to guide discrimination in this task, consistent with similar prior studies. Despite this, 52% of S1 units, including 73% of units in L4 and L2/3, encoded sequences at fast time scales (≤20 ms, mostly 5-10 ms), accurately reflecting single impulse kinematics. 17% of units, mostly in L5, showed weaker impulse responses and a slow firing rate increase during sequences. However, these units did not effectively integrate whisker impulses, but instead combined weak impulse responses with a distinct, slow signal correlated to behavioral choice. A neural decoder could identify sequences from fast unit spike trains and behavioral choice from slow units. Thus, S1 encoded fast time scale whisker input without substantial temporal integration across whisker impulses. PMID:27574970

  15. On the Absence of EUV Emission from Comet C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Bryans, Paul; Pesnell, W. Dean

    2016-05-01

    When the sungrazing comet C/2012 S1 (ISON) made its perihelion passage within two solar radii of the Sun’s surface, it was expected to be a bright emitter at extreme ultraviolet (EUV) wavelengths. However, despite solar EUV telescopes repointing to track the orbit of the comet, no emission was detected. This “null result” is interesting in its own right, offering the possibility of placing limits on the size and composition of the nucleus. We explain the lack of detection by considering the properties of the comet and the solar atmosphere that determine the intensity of EUV emission from sungrazing comets. By comparing these properties with those of sungrazing comet C/2011 W3 (Lovejoy), which did emit in the EUV, we conclude that the primary factor resulting in non-detectable EUV emission from C/2012 S1 (ISON) was an insufficiently large nucleus. We conclude that the radius of C/2012 S1 (ISON) was at least a factor of four less than that of C/2011 W3 (Lovejoy). This is consistent with white-light observations in the days before perihelion that suggested the comet was dramatically reducing in size on approach.

  16. Application of the S=1 underscreened Anderson lattice model to Kondo uranium and neptunium compounds

    NASA Astrophysics Data System (ADS)

    Thomas, Christopher; da Rosa Simões, Acirete S.; Iglesias, J. R.; Lacroix, C.; Perkins, N. B.; Coqblin, B.

    2011-01-01

    Magnetic properties of uranium and neptunium compounds showing the coexistence of the Kondo screening effect and ferromagnetic order are investigated within the Anderson lattice Hamiltonian with a two-fold degenerate f level in each site, corresponding to 5f2 electronic configuration with S=1 spins. A derivation of the Schrieffer-Wolff transformation is presented and the resulting Hamiltonian has an effective f-band term, in addition to the regular exchange Kondo interaction between the S=1 f spins and the s=1/2 spins of the conduction electrons. The resulting effective Kondo lattice model can describe both the Kondo regime and a weak delocalization of the 5f electrons. Within this model we compute the Kondo and Curie temperatures as a function of model parameters, namely the Kondo exchange interaction constant JK, the magnetic intersite exchange interaction JH, and the effective f bandwidth. We deduce, therefore, a phase diagram of the model which yields the coexistence of the Kondo effect and ferromagnetic ordering and also accounts for the pressure dependence of the Curie temperature of uranium compounds such as UTe.

  17. Cloning and characterization of a gene from Rhizobium melilotii 2011 coding for ribosomal protein S1.

    PubMed Central

    Schnier, J; Thamm, S; Lurz, R; Hussain, A; Faist, G; Dobrinski, B

    1988-01-01

    A 7 kb chromosomal DNA fragment from R. melilotii was cloned, which complemented temperature-sensitivity of an E. coli amber mutant in rpsA, the gene for ribosomal protein S1 (ES1). From complementation and maxicell analysis a 58 kd protein was identified as the homolog of protein S1 (RS1). DNA sequence analysis of the R. melilotii rpsA gene identified a protein of 568 amino acids, which showed 47% identical amino acid homology to protein S1 from E. coli. The RS1 protein lacked the two Cys residues which had been reported to play an important role for the function of ES1. Two repeats containing Shine-Dalgarno sequences were identified upstream of the structural gene. Binding studies with RNA polymerase from E. coli and Pseudomonas putida located one RNA-polymerase binding site close to the RS1 gene and another one several hundred basepairs upstream. One possible promoter was also identified by DNA sequence comparison with the corresponding E. coli promoter. Images PMID:3368316

  18. Probing the S1 specificity pocket of the aminopeptidases that generate antigenic peptides

    PubMed Central

    Zervoudi, Efthalia; Papakyriakou, Athanasios; Georgiadou, Dimitra; Evnouchidou, Irini; Gajda, Anna; Poreba, Marcin; Salvesen, Guy S.; Drag, Marcin; Hattori, Akira; Swevers, Luc; Vourloumis, Dionisios; Stratikos, Efstratios

    2014-01-01

    Synopsis ER aminopeptidase 1 (ERAP1), ER aminopeptidase 2 (ERAP2) and Insulin Regulated aminopeptidase (IRAP) are three homologous enzymes that play critical roles in the generation of antigenic peptides. These aminopeptidases excise amino acids from N-terminally extended precursors of antigenic peptides in order to generate the correct length epitopes for binding onto MHC class I molecules. The specificity of these peptidases can affect antigenic peptide selection, but has not yet been investigated in detail. In the present study we utilized a collection of 82 fluorogenic substrates to define a detailed selectivity profile for each of the three enzymes and to probe structural and functional features of the primary specificity (S1) pocket. Molecular modeling of the three S1 pockets reveals substrate-enzyme interactions that are critical determinants for specificity. The substrate selectivity profiles suggest that IRAP largely combines the S1 specificity of ERAP1 and ERAP2, consistent with its proposed biological function. IRAP however, does not achieve this dual specificity by simply combining structural features of ERAP1 and 2, but rather by a unique amino acid change at position 541. Our results provide insights on antigenic peptide selection and may prove valuable in designing selective inhibitors or activity markers for this class of enzymes. PMID:21314638

  19. Observations of sodium in the coma of Comet C/2012 S1 (ISON) during outburst

    NASA Astrophysics Data System (ADS)

    Schmidt, Carl A.; Johnson, Robert E.; Baumgardner, Jeffrey; Mendillo, Michael

    2015-02-01

    Prior to disintegration near its 2.7 R⊙ perihelion, the dynamically new Comet C/2012 S1(ISON) briefly exhibited resonantly scattered sodium emission at the 5890 Å and 5896 Å D lines. In this work, we report a rapid increase in sodium production of >3× between observations made only one day apart and the first observations of cometary sodium during an outburst. Mean Na production is estimated at 1.6 ± 0.3 × 1023 atoms s-1 on UT 19.5 Nov 2013 and 5.8 ± 1 × 1023 atoms s-1 on UT 20.5. At a heliocentric distance of 0.44 AU, the anti-sunward Na tail was detected >106 km from the nucleus. Surprisingly, these production rates are well below those of any previously determined when Na is seen from a comet. Accurately reproducing the emission in the Na tail on UT 20.5 Nov 2013 requires a source near the nucleus that varies with time due to the outburst. Data prior to outburst one day earlier can be reproduced if nearly half of total sodium production is attributed to an extended source such as dust grains. This suggests sources of sodium vapor in cometary coma are sensitive to the dust to gas ratio.

  20. [A Case Report of Advanced Gastric Cancer Demonstrating CR after Treatment with S-1 and Paclitaxel].

    PubMed

    Kudoh, Keisuke; Ogata, Kenichi; Ohchi, Tetsufumi; Ootao, Ryu; Koga, Yuki

    2015-11-01

    Here, we report a case of advanced gastric cancer that demonstrated CR after treatment with S-1 and paclitaxel. The patient was an 80-year-old woman with gastric cancer in whom upper gastrointestinal endoscopy (GIF) revealed a type 3 tumor in the cardia of the stomach that was pathologically diagnosed as a well-differentiated adenocarcinoma. Computed tomography showed no lymph node involvement or metastasis. Considering her advanced age and cardinal functional disorder, she was administered chemotherapy consisting of S-1 and paclitaxel. Depending on a state, a side effect, I changed a dose and inter-dose interval from head to foot and I treated it by foreign going to hospital and continued it. Gradual tumor reduction was observed on GIF (2011/1/25). CR was diagnosed without tumor disappearance, with accepted malignant findings on biopsy. The patient has now survived for 7 years 9 months after diagnosis. The present case demonstrates that combination therapy of S-1 and paclitaxel is safe and useful for patients with risk factors such as advanced age and underlying disease. PMID:26805267

  1. [Resection of Advanced Intrahepatic Cholangiocarcinoma after an Effective Response to S-1 and Gemcitabine Combination Therapy].

    PubMed

    Kuga, Yoshio; Moriya, Takashi; Fukuda, Saburo; Nishida, Toshihiro

    2016-06-01

    We report curative resection of an advanced intrahepatic cholangiocarcinoma that responded well to combined S-1 and gemcitabine chemotherapy(GS therapy). A 67-year-old woman was admitted to our hospital in July 2011 for upper right abdominal pain. She was diagnosed with intrahepatic cholangiocarcinoma with abdominal para-aortic lymph node metastasis on the basis of the computed tomography (CT) findings. She was treated with GS therapy. One course of S-1(80 mg/m(3)) consisted of the administration of the drug for 14 days, followed by 14 days of rest; GEM(1,000 mg/m(3)) was administered on days 1 and 15 after initiating S-1. After 2 courses of treatment, the sizes of the primary tumor and the lymph node metastasis were observed to be reduced on CT. In September, partial hepatectomy and regional lymph node dissection were performed. The patient subsequently received 22 postoperative courses of GS therapy. The patient's postoperative course was uneventful, and she remains free of recurrence 49 months since diagnosis. Therefore, GS therapy is a possible option for the management of advanced intrahepatic cholangiocarcinoma. PMID:27306819

  2. Short Time-Scale Sensory Coding in S1 during Discrimination of Whisker Vibrotactile Sequences

    PubMed Central

    Miyashita, Toshio; Lee, Daniel J.; Smith, Katherine A.; Feldman, Daniel E.

    2016-01-01

    Rodent whisker input consists of dense microvibration sequences that are often temporally integrated for perceptual discrimination. Whether primary somatosensory cortex (S1) participates in temporal integration is unknown. We trained rats to discriminate whisker impulse sequences that varied in single-impulse kinematics (5–20-ms time scale) and mean speed (150-ms time scale). Rats appeared to use the integrated feature, mean speed, to guide discrimination in this task, consistent with similar prior studies. Despite this, 52% of S1 units, including 73% of units in L4 and L2/3, encoded sequences at fast time scales (≤20 ms, mostly 5–10 ms), accurately reflecting single impulse kinematics. 17% of units, mostly in L5, showed weaker impulse responses and a slow firing rate increase during sequences. However, these units did not effectively integrate whisker impulses, but instead combined weak impulse responses with a distinct, slow signal correlated to behavioral choice. A neural decoder could identify sequences from fast unit spike trains and behavioral choice from slow units. Thus, S1 encoded fast time scale whisker input without substantial temporal integration across whisker impulses. PMID:27574970

  3. Correlation of charge, hydrophobicity, and structure with antimicrobial activity of S1 and MIRIAM peptides.

    PubMed

    Leptihn, Sebastian; Har, Jia Yi; Wohland, Thorsten; Ding, Jeak Ling

    2010-11-01

    Antimicrobial peptides are key elements of the innate immune system. Many of them interact with membranes of bacteria leading to perturbation of the lipid bilayer and eventually to inactivation of the pathogen. The emergence of multidrug-resistant bacteria has necessitated innovations of new and more powerful classes of antimicrobials. Here we present the in-depth study of an antimicrobial peptide, MIRIAM, derived from Sushi1 (S1), a well-characterized peptide from the horseshoe crab. MIRIAM interacts strongly with negatively charged lipids, forming an α-helical structure. MIRIAM was found to neutralize LPS and kill Gram-negative bacteria with high efficiency, while not releasing LPS. The promising therapeutic potential of MIRIAM is shown by hemolytic assays, which demonstrate that eukaryotic membranes are unaffected at bactericidal concentrations. Nanoparticle-conjugated MIRIAM used in single-molecule fluorescence and electron microscopy experiments showed that MIRIAM targets bacterial membranes to kill bacteria similarly to parental S1. Furthermore, fragments derived from MIRIAM and S1 provided insights on their molecular mechanisms of action, in particular, the relationships of functional motifs comprised by charge, hydrophobicity, and structure within each peptide. We conclude that the combination of charge, hydrophobicity, and length of the peptide is important. A close interaction of amino acids in a single molecule in a carefully balanced ensemble of sequence position and secondary structure is crucial. PMID:20873868

  4. MMP2 and MMP9 participate in S1P-induced invasion of follicular ML-1 thyroid cancer cells.

    PubMed

    Kalhori, Veronica; Törnquist, Kid

    2015-03-15

    The bioactive lipid sphingosine-1-phosphate (S1P) has emerged as a potent inducer of cancer cell migration and invasion. Previously, we have shown that S1P induces invasion of ML-1 follicular thyroid cancer cells via S1P receptors 1 and 3 (S1P1,3). Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes used by cells for degradation of the extracellular matrix during invasion and migration. In the present study, we examined the role of MMP2 and MMP9 for S1P-induced invasion of ML-1 cells, and found that S1P regulates the secretion and activity of MMP2 and MMP9 via S1P1,3. Both pharmacological inhibitors and siRNA knockdown of MMP2 and MMP9 could attenuate S1P-induced invasion. Additionally, we show that calpains and Rac1 mediate S1P-induced secretion of MMP2 and MMP9. In conclusion, MMP2 and MMP9 participate in S1P-evoked follicular ML-1 thyroid cancer cell invasion. PMID:25643979

  5. THE S1 SHELL AND INTERSTELLAR MAGNETIC FIELD AND GAS NEAR THE HELIOSPHERE

    SciTech Connect

    Frisch, Priscilla C.

    2010-05-10

    Many studies of the Loop I magnetic superbubble place the Sun at the edges of the bubble. One recent study models the polarized radio continuum of Loop I as two magnetic shells with the Sun embedded in the rim of the 'S1' shell. If the Sun is in such a shell, it should be apparent in both the local interstellar magnetic field and the distribution of nearby interstellar material. The properties of these subshells are compared to the interstellar magnetic field and the distribution of interstellar Fe{sup +} and Ca{sup +} within {approx}55 pc of the Sun. Although the results are not conclusive, the interstellar magnetic field direction obtained from polarized stars within {approx}30 pc is consistent with the interstellar magnetic field direction of the S1 shell. The distribution of nearby interstellar Fe{sup +} with log N(Fe{sup +}) < 12.5 cm{sup -2} is described equally well by a uniform distribution or an origin in spherical shell-like features. Higher column densities of Fe{sup +} (log N(Fe{sup +})>12.5 cm{sup -2}) tend to be better described by the path length of the sightline through the S1 and S2 subshells. Column densities of the recombinant ion Ca{sup +} are found to increase with the strength of the interstellar radiation field, rather than with star distance or total pathlength through the two magnetic subshells. The ion Ca{sup +} cannot be used to trace the distribution of local interstellar gas unless the spatial variations in the radiation field are included in the calculation of the ionization balance, in addition to possible abundance variations. The result is that a model of Loop I as composed of two spherical magnetic subshells remains a viable description of the distribution of nearby low density interstellar medium, but is not yet proven.

  6. Experimental design and environmental parameters affect Rhodospirillum rubrum S1H response to space flight.

    PubMed

    Mastroleo, Felice; Van Houdt, Rob; Leroy, Baptiste; Benotmane, M Abderrafi; Janssen, Ann; Mergeay, Max; Vanhavere, Filip; Hendrickx, Larissa; Wattiez, Ruddy; Leys, Natalie

    2009-12-01

    In view of long-haul space exploration missions, the European Space Agency initiated the Micro-Ecological Life Support System Alternative (MELiSSA) project targeting the total recycling of organic waste produced by the astronauts into oxygen, water and food using a loop of bacterial and higher plant bioreactors. In that purpose, the alpha-proteobacterium, Rhodospirillum rubrum S1H, was sent twice to the International Space Station and was analyzed post-flight using a newly developed R. rubrum whole genome oligonucleotide microarray and high throughput gel-free proteomics with Isotope-Coded Protein Label technology. Moreover, in an effort to identify a specific response of R. rubrum S1H to space flight, simulation of microgravity and space-ionizing radiation were performed on Earth under identical culture set-up and growth conditions as encountered during the actual space journeys. Transcriptomic and proteomic data were integrated and permitted to put forward the importance of medium composition and culture set-up on the response of the bacterium to space flight-related environmental conditions. In addition, we showed for the first time that a low dose of ionizing radiation (2 mGy) can induce a significant response at the transcriptomic level, although no change in cell viability and only a few significant differentially expressed proteins were observed. From the MELiSSA perspective, we could argue the effect of microgravity to be minimized, whereas R. rubrum S1H could be more sensitive to ionizing radiation during long-term space exploration mission. PMID:19571896

  7. Mutational analysis of hepatitis B virus pre-S1 (9-24) fusogenic peptide.

    PubMed

    Liu, Qiushi; Somiya, Masaharu; Shimada, Naohiko; Sakamoto, Wakako; Yoshimoto, Nobuo; Iijima, Masumi; Tatematsu, Kenji; Nakai, Tadashi; Okajima, Toshihide; Maruyama, Atsushi; Kuroda, Shuńichi

    2016-05-27

    A hollow nanoparticle known as a bio-nanocapsule (BNC) consisting of hepatitis B virus (HBV) envelope L protein and liposome (LP) can encapsulate drugs and genes and thereby deliver them in vitro and in vivo to human hepatic tissues, specifically by utilizing the HBV-derived infection machinery. Recently, we identified a low pH-dependent fusogenic domain at the N-terminal part of the pre-S1 region of the HBV L protein (amino acid residues 9 to 24; NPLGFFPDHQLDPAFG), which shows membrane destabilizing activity (i.e., membrane fusion, membrane disruption, and payload release) upon interaction with target LPs. In this study, instead of BNC and HBV, we generated LPs displaying a mutated form of the pre-S1 (9-24) peptide, and performed a membrane disruption assay using target LPs containing pyranine (fluorophore) and p-xylene-bis (N-pyridinium bromide) (DPX) as a quencher. The membrane disruption activity was found to correlate with the hydrophobicity of the whole structure, while the peptide retained a random-coil structure even under low pH condition. One large hydrophobic cluster (I) and one small hydrophobic cluster (II) residing in the peptide would be connected by the protonation of residues D16 and D20, and thereby exhibit strong membrane disruption activity in a low pH-dependent manner. Furthermore, the introduction of a positively charged residue enhanced the activity significantly, suggesting that a sole positively charged residue (H17) may be important for the interaction with target LPs by electrostatic interaction. Collectively, these results suggest that the pre-S1 (9-24) peptide may be involved in the endosomal escape of the BNC's payloads, as well as in the HBV uncoating process. PMID:27120459

  8. SU(2s+1) symmetry and nonlinear dynamics of high spin magnets

    SciTech Connect

    Kovalevsky, M.Y. Glushchenko, A.V.

    2014-10-15

    The article is devoted to the description of dynamics of magnets with arbitrary spin on the basis of the Hamiltonian formalism. The relationship of quantum states and magnetic degrees of freedom has been considered. Subalgebras of Poisson bracket of magnetic values for spin s=1/2; 1; 3/2 have been established. We have obtained non-linear dynamic equations for the normal and degenerate non-equilibrium states of high-spin magnets with the SO(3), SU(4), SU(2)×SU(2), SU(3), SO(4), SO(5) symmetries of exchange interaction. The connection between models of magnetic exchange energy and the Casimir invariants has been discussed.

  9. Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor.

    PubMed

    Maize, Kimberly M; Kurbanov, Elbek K; Johnson, Rodney L; Amin, Elizabeth Ambrose; Finzel, Barry C

    2015-12-21

    The Bacillus anthracis lethal factor (LF) is one component of a tripartite exotoxin partly responsible for persistent anthrax cytotoxicity after initial bacterial infection. Inhibitors of the zinc metalloproteinase have been investigated as potential therapeutic agents, but LF is a challenging target because inhibitors lack sufficient selectivity or possess poor pharmaceutical properties. These structural studies reveal an alternate conformation of the enzyme, induced upon binding of specific inhibitors, that opens a previously unobserved deep pocket termed S1'(∗) which might afford new opportunities to design selective inhibitors that target this subsite. PMID:26578066

  10. Varieties of Abelian mirror symmetry on {R}{{P}}^2× {{S}}^1

    NASA Astrophysics Data System (ADS)

    Mori, Hironori; Tanaka, Akinori

    2016-02-01

    We study 3d mirror symmetry with loop operators, Wilson loop and Vortex loop, and multi-flavor mirror symmetry through utilizing the {R}{{P}}^2× {{S}}^1 index formula. The key identity which makes the above description work well is the mod 2 version of the Fourier analysis, and we study such structure, the S-operation in the context of a SL(2,{Z}) action on 3d SCFTs. We observed that two types of the parity conditions basically associated with gauge symmetries which we call {P} -type and {C}{P} -type are interchanged under mirror symmetry. We will also comment on the T-operation.

  11. Amplification of S-1 Spheromak current by an inductive current transformer

    SciTech Connect

    Jardin, S.C.; Janos, A.; Yamada, M.

    1985-11-01

    We attempt to predict the consequences of adding an inductive current transformer (OH Transformer) to the present S-1 Spheromak experiment. Axisymmetric modeling with only classical dissipation shows an increase of toroidal current and a shrinking and hollowing of the current channel, conserving toroidal flux. These unstable profiles will undergo helical reconnection, conserving helicity K = ..integral.. A-vector x B-vector d tau while increasing the toroidal flux and decreasing the poloidal flux so that the plasma relaxes toward the Taylor state. This flux rearrangement is modeled by a new current viscosity term in the mean-field Ohm's law which conserves helicity and dissipates energy.

  12. Exciton mobility edge in CdS 1-xSe x solid solutions

    NASA Astrophysics Data System (ADS)

    Permogorov, S.; Reznitsky, A.; Verbin, S.; Lysenko, V.

    1983-07-01

    Low temperature emission spectra of localized excitons in CdS 1-xSe x solid solutions under the monochromatic excitation with tunable laser have been studied. It has been found that the luminescence of localized excitons has a high degree of linear polarization with respect to the polarization direction of exciting light. This polarization reflects the "hidden" anisotropy of macroscopically isotropic localized exciton system and strongly depends on the frequency of exciting light. Study of this dependence has permitted for the first time a determination of position of the "mobility edge" for exciton migration in disordered semiconductor solid solution.

  13. Light-induced magnetization in a spin S =1 easy-plane antiferromagnetic chain

    NASA Astrophysics Data System (ADS)

    Herbrych, J.; Zotos, X.

    2016-04-01

    The time evolution of magnetization induced by circularly polarized light in an S =1 Heisenberg chain with large easy-plane anisotropy is studied numerically and analytically. Results at constant light frequency Ω =Ω0 are interpreted in terms of absorption lines of the electronic spin resonance spectrum. The application of time-dependent frequency Ω =Ω (t ) light, so called chirping, is shown to be an efficient procedure in order to obtain within a short time a large, controlled value of the magnetization Mz. Furthermore, comparison with a two-level model provides a qualitative understanding of the induced magnetization process.

  14. Inclusive jet cross section at radical s = 1. 8 TeV

    SciTech Connect

    Hessing, T.L. . Dept. of Physics)

    1990-05-01

    The inclusive jet cross section at {radical}s = 1.8 TeV has been measured at the Fermilab Tevatron Collider. This measurement spans approximately 7 orders of magnitude in cross section and contains jets ranging from 30 GeV to over 400 GeV in transverse energy (E{sub t}). Comparisons have been made to QCD at both order {alpha}{sub s}{sup 2} and {alpha}{sub s}{sup 3}. 5 refs., 3 figs., 2 tabs.

  15. Observation of an Exotic S = +1 Baryon in Exclusive Photoproduction from the Deuteron

    SciTech Connect

    Stepan Stepanyan; Kenneth Hicks; Daniel Carman; Evgueni Pasyuk; Reinhard Schumacher; Elton Smith; David Tedeschi; Luminita Todor

    2003-12-19

    In an exclusive measurement of the reaction {gamma}d {yields} K{sup +} K{sup -} p n, a narrow peak that can be attributed to an exotic baryon with strangeness S = +1 is seen in the K{sup +}n invariant mass spectrum. The peak is at 1542 {+-} 5 MeV/c{sup 2} with a measured width of 21 MeV/c{sup 2} FWHM, equivalent to the experimental invariant mass resolution. The statistical significance of the peak is 5.3 {+-} 0.5 {sigma} for a Gaussian peak shape on top of a smooth background.

  16. Mechanisms for spin supersolidity in S=(1/2) spin-dimer antiferromagnets

    SciTech Connect

    Picon, J.-D.; Albuquerque, A. F.; Schmidt, K. P.; Laflorencie, N.; Troyer, M.; Mila, F.

    2008-11-01

    Using perturbative expansions and the contractor renormalization (CORE) algorithm, we obtain effective hard-core bosonic Hamiltonians describing the low-energy physics of S=1/2 spin-dimer antiferromagnets known to display supersolid phases under an applied magnetic field. The resulting effective models are investigated by means of mean-field analysis and quantum Monte Carlo simulations. A 'leapfrog mechanism,' through means of which extra singlets delocalize in a checkerboard-solid environment via correlated hoppings, is unveiled that accounts for the supersolid behavior.

  17. Properties of digital 1/3-octave filters implemented according to ANSI S1.11

    NASA Astrophysics Data System (ADS)

    Geras, Antonina; Starecki, Tomasz

    The paper presents results of investigation into properties of digital filters implemented in compliance with ANSI S1.11 Standard: Octave-Band and Fractional-Octave Band Analog and Digital Filters. The discussed solutions are digital one-third-octave IIR filters with Direct Form I topology. Performed simulations showed that the filters exhibit strong problems with stability, especially in the case of low center frequency filters. Another problem clearly visible in all investigated structures was poor attenuation at the frequencies above the passband. Although the filters were implemented according to the ANSI standard, none of them met all of the requirements of the standard.

  18. Formation, Redox-Controled Preservation, and Interruption of Organic-rich Sapropel S1 sediments

    NASA Astrophysics Data System (ADS)

    De Lange, Gert J.; Hennekam, Rick; Goudeau, Marie-Louise; Filippidi, Amalia

    2015-04-01

    Distinct, organic-rich units (sapropels) occur in Mediterraneran sediments in a repetitive, climate-controled way. Their deposition is thought to be precession-related and to be associated with humid climate conditions. The last humid period from 11 - 5 kyr 14C ago, occurred simultaneous with a sustained circum-Mediterranean wet period. Within that period, the most recent sapropel (S1) formed synchronously between 9.8 and 5.7 14C ky BP at all water depths greater than a few hundred metres. As a consequence of increased fresh water (monsoon) input, surface waters had a reduced salinity and concomitantly the deep (> 1.8 km) eastern Mediterranean Sea was devoid of oxygen during 4,000 years of S1. This has resulted in a differential basin-wide preservation of S1 determined by water depth, as a result of different ventilation/climate-related redox conditions above and below 1.8 km. The end of this period is marked by a basin-wide high sedimentary manganese-oxide peak that represents an abrupt re-ventilation of the deep-water at 5.7 kyr. The sustaining oxic conditions thereafter have resulted in a downward progressing oxidation-front that is not only characterized by the degradation of most organic matter over its active pathway, but also by the built-up of manganese oxide. The latter has resulted in a secondary Mn-peak below the first, upper, ventilation Mn-peak. Apart from the major re-ventilation event at the end of sapropel S1 formation, also other, short-term ventilation events appear to have occurred during its formation, notably the 8.2 ka event. This potentially basin-wide event is particularly noticeable at relatively shallow near-coastal sites of high sedimentation rates. It marks a brief episode of not only re-oxygenated deep water thus reduced preservation, but also decreased primary productivity thus nutrient supply. This 8.2 cal ka BP interruption event is thought to be related to enhanced deep water formation in the Aegean or Adriatic due to a period of

  19. Redox-Controled Preservation of Mediterranean Sapropel S1 deposits during Formation and Interruption

    NASA Astrophysics Data System (ADS)

    De Lange, Gert J.; Filippidi, Amalia; Goudeau, Marie-Louise; Hennekam, Rick

    2016-04-01

    Organic-rich units (sapropels) occur in Mediterraneran sediments in a repetitive, climate-controled way. Their deposition is thought to be precession-related and to be associated with humid climate conditions. The last humid period from 11 - 5 kyr 14C ago, occurred simultaneous with a sustained circum-Mediterranean wet period and vegetated Sahara. Within that period, the most recent sapropel (S1) formed synchronously between 9.8 and 5.7 14C ky BP at all water depths greater than a few hundred metres. As a consequence of increased fresh water (monsoon) input, surface waters had a reduced salinity and concomitantly the deep (> 1.8 km) eastern Mediterranean Sea was devoid of oxygen during 4,000 years of S1 formation. This has resulted in a differential basin-wide preservation of S1sediments determined by water depth, as a result of different ventilation/climate-related redox conditions above and below 1.8 km. The end of this period is marked by a basin-wide high sedimentary manganese-oxide peak that represents an abrupt re-ventilation of the deep-water at 5.7 kyr. The sustaining oxic conditions thereafter have resulted in a downward progressing oxidation-front that is not only characterized by the degradation of most organic matter over its active pathway, but also by the built-up of manganese oxide. The latter has resulted in a secondary diagenetic Mn-peak below the first, upper, ventilation Mn-peak. Apart from the major re-ventilation event at the end of sapropel S1 formation, also other, short-term ventilation events appear to have occurred during its formation, notably during the 8.2 ka event. This potentially basin-wide event is particularly noticeable at relatively shallow near-coastal sites of high sedimentation rates. It marks a brief episode of not only re-oxygenated deep water thus reduced preservation, but also decreased primary productivity thus nutrient supply. This 8.2 cal ka BP interruption event is thought to be related to enhanced deep water formation

  20. Complete genome sequence of Ignisphaera aggregans type strain (AQ1.S1T)

    SciTech Connect

    Goker, Markus; Held, Brittany; Lapidus, Alla L.; Nolan, Matt; Spring, Stefan; Yasawong, Montri; Lucas, Susan; Glavina Del Rio, Tijana; Tice, Hope; Cheng, Jan-Fang; Goodwin, Lynne A.; Tapia, Roxanne; Pitluck, Sam; Liolios, Konstantinos; Ivanova, N; Mavromatis, K; Mikhailova, Natalia; Pati, Amrita; Palaniappan, Krishna; Brambilla, Evelyne-Marie; Land, Miriam L; Hauser, Loren John; Chang, Yun-Juan; Jeffries, Cynthia; Brettin, Thomas S; Detter, J. Chris; Han, Cliff; Rohde, Manfred; Sikorski, Johannes; Woyke, Tanja; Bristow, James; Eisen, Jonathan; Markowitz, Victor; Hugenholtz, Philip; Kyrpides, Nikos C; Klenk, Hans-Peter

    2010-01-01

    Ignisphaera aggregans Niederberger et al. 2006 is the type and sole species of genus Ignisphaera. This archaeal species is characterized by a cocci-shaped, strictly anaerobic, moderately acidophilic, heterotrophic hyperthermophile and fermentative phenotype. The type strain AQ1.S1T was isolated from a near neutral, boiling spring in Kuirau Park, Rotorua, New Zealand. This is the first completed genome sequence of the genus Ignisphaera and the fifth genome (fourth type strain) sequence in the family Desulfurococcaceae. The 1,875,953 bp long genome with its 2,061 protein-coding and 52 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project.

  1. Electrical and Optical Properties of the CuGa(S1-xSex)2 System

    NASA Astrophysics Data System (ADS)

    Matsushita, Hiroaki; Endo, Saburo; Nakanishi, Hisayuki; Nomura, Shigetaka; Irie, Taizo

    1990-03-01

    The mixed crystal system CuGa(S1-xSex)2 was prepared by the normal freezing method. The compositional dependence of the lattice constants and the optical band gap obeyed Vergard’s law. The phase diagram of this system was studied by DTA measurement. An orange photoluminescence was observed for x{≤q}0.5 after annealing in vacuum. It was confirmed that the emission was due to D-A pair recombinations, and an increase of S-vacancy caused an increase of photoluminescence intensity. The electrical resistivity was also affected by S-vacancy.

  2. Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor

    SciTech Connect

    Maize, Kimberly M.; Kurbanov, Elbek K.; Johnson, Rodney L.; Amin, Elizabeth Ambrose; Finzel, Barry C.

    2015-11-11

    The Bacillus anthracis lethal factor (LF) is one component of a tripartite exotoxin partly responsible for persistent anthrax cytotoxicity after initial bacterial infection. Inhibitors of the zinc metalloproteinase have been investigated as potential therapeutic agents, but LF is a challenging target because inhibitors lack sufficient selectivity or possess poor pharmaceutical properties. These structural studies reveal an alternate conformation of the enzyme, induced upon binding of specific inhibitors, that opens a previously unobserved deep pocket termed S1'* which might afford new opportunities to design selective inhibitors that target this subsite.

  3. Minimally invasive L5-S1 oblique lumbar interbody fusion with anterior plate.

    PubMed

    Pham, Martin H; Jakoi, Andre M; Hsieh, Patrick C

    2016-07-01

    Lumbar interbody fusion is an important technique for the treatment of degenerative disc disease and degenerative scoliosis. The oblique lumbar interbody fusion (OLIF) establishes a minimally invasive retroperitoneal exposure anterior to the psoas and lumbar plexus. In this video case presentation, the authors demonstrate the techniques of the OLIF at L5-S1 performed on a 69-year-old female with degenerative scoliosis as one component of an overall strategy for her deformity correction. The video can be found here: https://youtu.be/VMUYWKLAl0g . PMID:27364428

  4. Strangeness S =-1 hyperon-nucleon scattering in covariant chiral effective field theory

    NASA Astrophysics Data System (ADS)

    Li, Kai-Wen; Ren, Xiu-Lei; Geng, Li-Sheng; Long, Bingwei

    2016-07-01

    Motivated by the successes of covariant baryon chiral perturbation theory in one-baryon systems and in heavy-light systems, we study relevance of relativistic effects in hyperon-nucleon interactions with strangeness S =-1 . In this exploratory work, we follow the covariant framework developed by Epelbaum and Gegelia to calculate the Y N scattering amplitude at leading order. By fitting the five low-energy constants to the experimental data, we find that the cutoff dependence is mitigated, compared with the heavy-baryon approach. Nevertheless, the description of the experimental data remains quantitatively similar at leading order.

  5. A possible detection of Jupiter's northern auroral S1(1) H2 quadrupole line emission

    NASA Technical Reports Server (NTRS)

    Trafton, L.; Carr, J.; Lester, D.; Harvey, P.

    1988-01-01

    An upper limit is presently determined for the mean intensity of the Jupiter northern Auroral UV/thermal hot spot's S1(1) H2 quadrupole emission, over an 8 sq arcsec illuminated beam; the value obtained is 4.2 X 10 to the -6th W/sq m per sr. It is suggested that the nonradiative deexitation of the H2 molecules via collisions with H may have been underestimated by Kim and Maguire (1986), due to uncertainties concerning auroral H density.

  6. S-1 and S-2-alar-iliac screw fixation via intraoperative navigation.

    PubMed

    Pham, Martin H; Jakoi, Andre M; Hsieh, Patrick C

    2016-07-01

    Adult deformity patients often require fixation to the sacrum and pelvis for construct stability and improved fusion rates. Although certain sacropelvic fixation techniques can be challenging, the availability of intraoperative navigation has made many of these techniques more feasible. In this video case presentation, the authors demonstrate the techniques of S-1 bicortical screw and S-2-alar-iliac screw fixation under intraoperative navigation in a 67-year-old female. This instrumentation placement was part of an overall T-10-pelvis construct for the correction of adult spinal deformity. The video can be found here: https://youtu.be/3HZo-80jQr8 . PMID:27364427

  7. Fingolimod: direct CNS effects of sphingosine 1-phosphate (S1P) receptor modulation and implications in multiple sclerosis therapy

    PubMed Central

    Groves, Aran; Kihara, Yasuyuki; Chun, Jerold

    2013-01-01

    Fingolimod is the first oral disease-modifying therapy approved for relapsing forms of multiple sclerosis (MS). Following phosphorylation in vivo, the active agent, fingolimod phosphate (fingolimod-P), acts as a sphingosine 1-phosphate (S1P) receptor modulator, binding with high affinity to four of the five known S1P receptors (S1P1, S1P3, S1P4 and S1P5). The mechanism of action of fingolimod in MS has primarily been considered as immunomodulatory, whereby fingolimod-P modulates S1P1 on lymphocytes, selectively retaining autoreactive lymphocytes in lymph nodes to reduce damaging infiltration into the central nervous system (CNS). However, emerging evidence indicates that fingolimod has direct effects in the CNS in MS. For example, in the MS animal model of experimental autoimmune encephalomyelitis (EAE), fingolimod is highly efficacious in both a prophylactic and therapeutic setting, yet becomes ineffective in animals selectively deficient for S1P1 on astrocytes, despite maintained normal immunologic receptor expression and functions, and S1P-mediated immune activities. Here, we review S1P signalling effects relevant to MS in neural cell types expressing S1P receptors, including astrocytes, oligodendrocytes, neurons, microglia and dendritic cells. The direct effects of fingolimod on these CNS cells observed in preclinical studies are discussed in view of the functional consequences of reducing neurodegenerative processes and promoting myelin preservation and repair. The therapeutic implications of S1P modulation in the CNS are considered in terms of the clinical outcomes of MS, such as reducing MS-related brain atrophy, and other CNS disorders. Additionally, we briefly outline other existing and investigational MS therapies that may also have effects in the CNS. PMID:23518370

  8. Sphingosine-1-Phosphate Enhances Satellite Cell Activation in Dystrophic Muscles through a S1PR2/STAT3 Signaling Pathway

    PubMed Central

    Carlson, Morgan E.; Oskouian, Babak; Kumar, Ashok; Fyrst, Henrik; Zhang, Meng; Proia, Richard L.; Hoffman, Eric P.; Saba, Julie D.

    2012-01-01

    Sphingosine-1-phosphate (S1P) activates a widely expressed family of G protein-coupled receptors, serves as a muscle trophic factor and activates muscle stem cells called satellite cells (SCs) through unknown mechanisms. Here we show that muscle injury induces dynamic changes in S1P signaling and metabolism in vivo. These changes include early and profound induction of the gene encoding the S1P biosynthetic enzyme SphK1, followed by induction of the catabolic enzyme sphingosine phosphate lyase (SPL) 3 days later. These changes correlate with a transient increase in circulating S1P levels after muscle injury. We show a specific requirement for SphK1 to support efficient muscle regeneration and SC proliferation and differentiation. Mdx mice, which serve as a model for muscular dystrophy (MD), were found to be S1P-deficient and exhibited muscle SPL upregulation, suggesting that S1P catabolism is enhanced in dystrophic muscle. Pharmacological SPL inhibition increased muscle S1P levels, improved mdx muscle regeneration and enhanced SC proliferation via S1P receptor 2 (S1PR2)-dependent inhibition of Rac1, thereby activating Signal Transducer and Activator of Transcription 3 (STAT3), a central player in inflammatory signaling. STAT3 activation resulted in p21 and p27 downregulation in a S1PR2-dependent fashion in myoblasts. Our findings suggest that S1P promotes SC progression through the cell cycle by repression of cell cycle inhibitors via S1PR2/STAT3-dependent signaling and that SPL inhibition may provide a therapeutic strategy for MD. PMID:22606352

  9. ClpS1 Is a Conserved Substrate Selector for the Chloroplast Clp Protease System in Arabidopsis[C][W

    PubMed Central

    Nishimura, Kenji; Asakura, Yukari; Friso, Giulia; Kim, Jitae; Oh, Soo-hyun; Rutschow, Heidi; Ponnala, Lalit; van Wijk, Klaas J.

    2013-01-01

    Whereas the plastid caseinolytic peptidase (Clp) P protease system is essential for plant development, substrates and substrate selection mechanisms are unknown. Bacterial ClpS is involved in N-degron substrate selection and delivery to the ClpAP protease. Through phylogenetic analysis, we show that all angiosperms contain ClpS1 and some species also contain ClpS1-like protein(s). In silico analysis suggests that ClpS1 is the functional homolog of bacterial ClpS. We show that Arabidopsis thaliana ClpS1 interacts with plastid ClpC1,2 chaperones. The Arabidopsis ClpS1 null mutant (clps1) lacks a visible phenotype, and no genetic interactions with ClpC/D chaperone or ClpPR core mutants were observed. However, clps1, but not clpc1-1, has increased sensitivity to the translational elongation inhibitor chloramphenicol suggesting a link between translational capacity and ClpS1. Moreover, ClpS1 was upregulated in clpc1-1, and quantitative proteomics of clps1, clpc1, and clps1 clpc1 showed specific molecular phenotypes attributed to loss of ClpC1 or ClpS1. In particular, clps1 showed alteration of the tetrapyrrole pathway. Affinity purification identified eight candidate ClpS1 substrates, including plastid DNA repair proteins and Glu tRNA reductase, which is a control point for tetrapyrrole synthesis. ClpS1 interaction with five substrates strictly depended on two conserved ClpS1 residues involved in N-degron recognition. ClpS1 function, substrates, and substrate recognition mechanisms are discussed. PMID:23898032

  10. Sphingosine-1-phosphate enhances satellite cell activation in dystrophic muscles through a S1PR2/STAT3 signaling pathway.

    PubMed

    Loh, Kenneth C; Leong, Weng-In; Carlson, Morgan E; Oskouian, Babak; Kumar, Ashok; Fyrst, Henrik; Zhang, Meng; Proia, Richard L; Hoffman, Eric P; Saba, Julie D

    2012-01-01

    Sphingosine-1-phosphate (S1P) activates a widely expressed family of G protein-coupled receptors, serves as a muscle trophic factor and activates muscle stem cells called satellite cells (SCs) through unknown mechanisms. Here we show that muscle injury induces dynamic changes in S1P signaling and metabolism in vivo. These changes include early and profound induction of the gene encoding the S1P biosynthetic enzyme SphK1, followed by induction of the catabolic enzyme sphingosine phosphate lyase (SPL) 3 days later. These changes correlate with a transient increase in circulating S1P levels after muscle injury. We show a specific requirement for SphK1 to support efficient muscle regeneration and SC proliferation and differentiation. Mdx mice, which serve as a model for muscular dystrophy (MD), were found to be S1P-deficient and exhibited muscle SPL upregulation, suggesting that S1P catabolism is enhanced in dystrophic muscle. Pharmacological SPL inhibition increased muscle S1P levels, improved mdx muscle regeneration and enhanced SC proliferation via S1P receptor 2 (S1PR2)-dependent inhibition of Rac1, thereby activating Signal Transducer and Activator of Transcription 3 (STAT3), a central player in inflammatory signaling. STAT3 activation resulted in p21 and p27 downregulation in a S1PR2-dependent fashion in myoblasts. Our findings suggest that S1P promotes SC progression through the cell cycle by repression of cell cycle inhibitors via S1PR2/STAT3-dependent signaling and that SPL inhibition may provide a therapeutic strategy for MD. PMID:22606352

  11. Dynamics of vibrational relaxation in the S 1 state of carotenoids having 11 conjugated CC bonds

    NASA Astrophysics Data System (ADS)

    Hörvin Billsten, Helena; Zigmantas, Donatas; Sundström, Villy; Polívka, Tomáš

    2002-04-01

    Transient absorption spectra and kinetics in the 470-650 nm region were recorded for lycopene, β-carotene and zeaxanthin, all carotenoids with 11 conjugated double bonds, in two solvents with different polarity. Analysis of the red wing of the carotenoid S 1-S n transition revealed presence of a pronounced shoulder at early delay times. The kinetics recorded at this low-energy shoulder of the S 1-S n transition yields an additional decay component of 500-800 fs in addition to the main S 1 decay. This dynamics is ascribed to a vibrational relaxation in the S 1 state of the carotenoids.

  12. Defective sphingosine 1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation.

    PubMed

    Garris, Christopher S; Wu, Linfeng; Acharya, Swati; Arac, Ahmet; Blaho, Victoria A; Huang, Yingxiang; Moon, Byoung San; Axtell, Robert C; Ho, Peggy P; Steinberg, Gary K; Lewis, David B; Sobel, Raymond A; Han, David K; Steinman, Lawrence; Snyder, Michael P; Hla, Timothy; Han, May H

    2013-11-01

    Sphingosine 1-phosphate (S1P) signaling regulates lymphocyte egress from lymphoid organs into systemic circulation. The sphingosine phosphate receptor 1 (S1P1) agonist FTY-720 (Gilenya) arrests immune trafficking and prevents multiple sclerosis (MS) relapses. However, alternative mechanisms of S1P-S1P1 signaling have been reported. Phosphoproteomic analysis of MS brain lesions revealed S1P1 phosphorylation on S351, a residue crucial for receptor internalization. Mutant mice harboring an S1pr1 gene encoding phosphorylation-deficient receptors (S1P1(S5A)) developed severe experimental autoimmune encephalomyelitis (EAE) due to autoimmunity mediated by interleukin 17 (IL-17)-producing helper T cells (TH17 cells) in the peripheral immune and nervous system. S1P1 directly activated the Jak-STAT3 signal-transduction pathway via IL-6. Impaired S1P1 phosphorylation enhances TH17 polarization and exacerbates autoimmune neuroinflammation. These mechanisms may be pathogenic in MS. PMID:24076635

  13. Label-free fluorometric detection of S1 nuclease activity by using polycytosine oligonucleotide-templated silver nanoclusters.

    PubMed

    Wang, Lihui; Ma, Keke; Zhang, Yaodong

    2014-09-28

    S1 nuclease has an important function in DNA transcription, replication, recombination, and repair. A label-free fluorescent method for the detection of S1 nuclease activity has been developed using polycytosine oligonucleotide-templated silver nanoclusters (dC12-Ag NCs). In this assay, dC12 can function as both the template for the stabilization of Ag NCs and the substrate of the S1 nuclease. Fluorescent Ag NCs could be effectively formed using dC12 as the template without S1 nuclease. In the presence of S1 nuclease, dC12 is degraded to mono- or oligonucleotide fragments, thereby resulting in a reduction in fluorescence. S1 nuclease with an activity as low as 5×10(-8)Uμl(-1) (signal/noise=3) can be determined with a linear range of 5×10(-7) to 1×10(-3)Uμl(-1). The promising application of the proposed method in S1 nuclease inhibitor screening has been demonstrated using pyrophosphate as the model inhibitor. Furthermore, the S1 nuclease concentrations in RPMI 1640 cell medium were validated. The developed method for S1 nuclease is sensitive and facile because its operation does not require any complicated DNA labeling or laborious fluorescent dye synthesis. PMID:25263815

  14. Patterns of Sequence Divergence and Evolution of the S1 Orthologous Regions between Asian and African Cultivated Rice Species

    PubMed Central

    Gavory, Frédérick; Samain, Sylvie; Tohme, Joe; Ghesquière, Alain; Lorieux, Mathias

    2011-01-01

    A strong postzygotic reproductive barrier separates the recently diverged Asian and African cultivated rice species, Oryza sativa and O. glaberrima. Recently a model of genetic incompatibilities between three adjacent loci: S1A, S1 and S1B (called together the S1 regions) interacting epistatically, was postulated to cause the allelic elimination of female gametes in interspecific hybrids. Two candidate factors for the S1 locus (including a putative F-box gene) were proposed, but candidates for S1A and S1B remained undetermined. Here, to better understand the basis of the evolution of regions involved in reproductive isolation, we studied the genic and structural changes accumulated in the S1 regions between orthologous sequences. First, we established an 813 kb genomic sequence in O. glaberrima, covering completely the S1A, S1 and the majority of the S1B regions, and compared it with the orthologous regions of O. sativa. An overall strong structural conservation was observed, with the exception of three isolated regions of disturbed collinearity: (1) a local invasion of transposable elements around a putative F-box gene within S1, (2) the multiple duplication and subsequent divergence of the same F-box gene within S1A, (3) an interspecific chromosomal inversion in S1B, which restricts recombination in our O. sativa×O. glaberrima crosses. Beside these few structural variations, a uniform conservative pattern of coding sequence divergence was found all along the S1 regions. Hence, the S1 regions have undergone no drastic variation in their recent divergence and evolution between O. sativa and O. glaberrima, suggesting that a small accumulation of genic changes, following a Bateson-Dobzhansky-Muller (BDM) model, might be involved in the establishment of the sterility barrier. In this context, genetic incompatibilities involving the duplicated F-box genes as putative candidates, and a possible strengthening step involving the chromosomal inversion might participate to

  15. Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD

    SciTech Connect

    Barbieri, J.T.; Mende-Mueller, L.M.; Rappuoli, R.; Collier, R.J. )

    1989-11-01

    UV irradiation was shown to induce efficient transfer of radiolabel from nicotinamide-labeled NAD to a recombinant protein (C180 peptide) containing the catalytic region of the S-1 subunit of pertussis toxin. Incorporation of label from (3H-nicotinamide)NAD was efficient (0.5 to 0.6 mol/mol of protein) relative to incorporation from (32P-adenylate)NAD (0.2 mol/mol of protein). Label from (3H-nicotinamide)NAD was specifically associated with Glu-129. Replacement of Glu-129 with glycine or aspartic acid made the protein refractory to photolabeling with (3H-nicotinamide)NAD, whereas replacement of a nearby glutamic acid, Glu-139, with serine did not. Photolabeling of the C180 peptide with NAD is similar to that observed with diphtheria toxin and exotoxin A of Pseudomonas aeruginosa, in which the nicotinamide portion of NAD is transferred to Glu-148 and Glu-553, respectively, in the two toxins. These results implicate Glu-129 of the S-1 subunit as an active-site residue and a potentially important site for genetic modification of pertussis toxin for development of an acellular vaccine against Bordetella pertussis.

  16. Magnetic flux conversion and relaxation toward a minimum-energy state in S-1 spheromak plasmas

    SciTech Connect

    Janos, A.

    1985-09-01

    S-1 Spheromak currents and magnetic fluxes have been measured with Rogowski coils and flux loops external to the plasma. Toroidal plasma currents up to 350 kA and spheromak configuration lifetimes over 1.0 msec have been achieved at moderate power levels. The plasma formation in the S-1 Spheromak device is based on an inductive transfer of poloidal and toroidal magnetic flux from a toroidal ''flux core'' to the plasma. Formation is programmed to guide the configuration into a force-free, minimum-energy Taylor state. Properly detailed programming of the formation process is found not to be essential since plasmas adjust themselves during formation to a final equilibrium near the Taylor state. After formation, if the plasma evolves away from the stable state, then distinct relaxation oscillation events occur which restore the configuration to that stable state. The relaxation process involves reconnection of magnetic field lines, and conversion of poloidal to toroidal magnetic flux (and vice versa) has been observed and documented. The scaling of toroidal plasma current and toroidal magnetic flux in the plasma with externally applied currents is consistent with the establishment of a Taylor state after formation. In addition, the magnetic helicity is proportional to that injected from the flux core, independent of how that helicity is generated.

  17. S1 gene-based phylogeny of infectious bronchitis virus: An attempt to harmonize virus classification.

    PubMed

    Valastro, Viviana; Holmes, Edward C; Britton, Paul; Fusaro, Alice; Jackwood, Mark W; Cattoli, Giovanni; Monne, Isabella

    2016-04-01

    Infectious bronchitis virus (IBV) is the causative agent of a highly contagious disease that results in severe economic losses to the global poultry industry. The virus exists in a wide variety of genetically distinct viral types, and both phylogenetic analysis and measures of pairwise similarity among nucleotide or amino acid sequences have been used to classify IBV strains. However, there is currently no consensus on the method by which IBV sequences should be compared, and heterogeneous genetic group designations that are inconsistent with phylogenetic history have been adopted, leading to the confusing coexistence of multiple genotyping schemes. Herein, we propose a simple and repeatable phylogeny-based classification system combined with an unambiguous and rationale lineage nomenclature for the assignment of IBV strains. By using complete nucleotide sequences of the S1 gene we determined the phylogenetic structure of IBV, which in turn allowed us to define 6 genotypes that together comprise 32 distinct viral lineages and a number of inter-lineage recombinants. Because of extensive rate variation among IBVs, we suggest that the inference of phylogenetic relationships alone represents a more appropriate criterion for sequence classification than pairwise sequence comparisons. The adoption of an internationally accepted viral nomenclature is crucial for future studies of IBV epidemiology and evolution, and the classification scheme presented here can be updated and revised novel S1 sequences should become available. PMID:26883378

  18. Experimental signatures of spin liquid physics on the S=1/2 kagom'e lattice

    NASA Astrophysics Data System (ADS)

    Lee, Young

    2012-02-01

    I will describe our recent experimental progress on the quest to study novel ground states in frustrated magnets. New states of matter may be produced if quantum effects and frustration conspire to prevent the ground state from achieving classical order. Materials based on the kagom'e lattice appear to be ideal hosts for the possibility of a quantum spin liquid ground state in two-dimensions. I will discuss our work which includes single crystal growth, bulk characterization, and neutron scattering measurements of the S=1/2 kagom'e lattice material ZnCu3(OH)6Cl2 (also known as herbertsmithite). Recent susceptibility measurements on single crystals yield valuable information on the additional terms in the spin Hamiltonian beyond nearest neighbor Heisenberg exchange, and anomalous x-ray diffraction yields detailed information on the presence of a small amount of atomic impurities. Most interestingly, inelastic neutron scattering measurements of the spin correlations in a single crystal sample reveal a continuum of spinon excitations in this two-dimensional insulating magnet. We will discuss our results in relation to recent theories for spin liquid physics on the S=1/2 kagom'e lattice.

  19. Spectroscopic study on deuterated benzenes. III. Vibronic structure and dynamics in the S1 state

    NASA Astrophysics Data System (ADS)

    Kunishige, Sachi; Katori, Toshiharu; Kawabata, Megumi; Yamanaka, Takaya; Baba, Masaaki

    2015-12-01

    We observed the fluorescence excitation spectra and mass-selected resonance enhanced multiphoton ionization (REMPI) excitation spectra for the 6 01 , 6 01 10 1 , and 6 01 10 2 bands of the S1←S0 transition of jet-cooled deuterated benzene and assigned the vibronic bands of C6D6 and C6HD5. The 60 1 10 n (n = 0, 1, 2) and 00 0 transition energies were found to be dependent only on the number of D atoms (ND), which was reflected by the zero-point energy of each H/D isotopomer. In some isotopomers some bands, such as those of out-of-plane vibrations mixed with 611n, make the spectra complex. These included the 611021n level or combination bands with ν12 which are allowed because of reduced molecular symmetry. From the lifetime measurements of each vibronic band, some enhancement of the nonradiative intramolecular vibrational redistribution (IVR) process was observed. It was also found that the threshold excess energy of "channel three" was higher than the 6112 levels, which were similar for all the H/D isotopomers. We suggest that the channel three nonradiative process could be caused mainly by in-plane processes such as IVR and internal conversion at the high vibrational levels in the S1 state of benzene, although the out-of-plane vibrations might contribute to some degree.

  20. Unusual selection on the KIR3DL1/S1 natural killer cell receptor in Africans.

    PubMed

    Norman, Paul J; Abi-Rached, Laurent; Gendzekhadze, Ketevan; Korbel, Daniel; Gleimer, Michael; Rowley, Don; Bruno, Dan; Carrington, Christine V F; Chandanayingyong, Dasdayanee; Chang, Yih-Hsin; Crespí, Catalina; Saruhan-Direskeneli, Güher; Fraser, Patricia A; Hameed, Kamran; Kamkamidze, Giorgi; Koram, Kwadwo A; Layrisse, Zulay; Matamoros, Nuria; Milà, Joan; Park, Myoung Hee; Pitchappan, Ramasamy M; Ramdath, D Dan; Shiau, Ming-Yuh; Stephens, Henry A F; Struik, Siske; Verity, David H; Vaughan, Robert W; Tyan, Dolly; Davis, Ronald W; Riley, Eleanor M; Ronaghi, Mostafa; Parham, Peter

    2007-09-01

    Interactions of killer cell immunoglobulin-like receptors (KIRs) with major histocompatibility complex (MHC) class I ligands diversify natural killer cell responses to infection. By analyzing sequence variation in diverse human populations, we show that the KIR3DL1/S1 locus encodes two lineages of polymorphic inhibitory KIR3DL1 allotypes that recognize Bw4 epitopes of protein">HLA-A and HLA-B and one lineage of conserved activating KIR3DS1 allotypes, also implicated in Bw4 recognition. Balancing selection has maintained these three lineages for over 3 million years. Variation was selected at D1 and D2 domain residues that contact HLA class I and at two sites on D0, the domain that enhances the binding of KIR3D to HLA class I. HLA-B variants that gained Bw4 through interallelic microconversion are also products of selection. A worldwide comparison uncovers unusual KIR3DL1/S1 evolution in modern sub-Saharan Africans. Balancing selection is weak and confined to D0, KIR3DS1 is rare and KIR3DL1 allotypes with similar binding sites predominate. Natural killer cells express the dominant KIR3DL1 at a high frequency and with high surface density, providing strong responses to cells perturbed in Bw4 expression. PMID:17694054

  1. Epidermal surface antigen (MS17S1) is highly conserved between mouse and human.

    PubMed

    Cho, Y J; Chema, D; Moskow, J J; Cho, M; Schroeder, W T; Overbeek, P; Buchberg, A M; Duvic, M

    1995-05-20

    A mouse monoclonal antibody ECS-1 raised to human keratinocytes detects a 35-kDa epidermal surface antigen (ESA) and causes keratinocyte dissociation in vitro. ECS-1 stains skin of 16-day mouse embryo and 8- to 9-week human fetus. Mouse Esa cDNA encodes a 379-amino-acid protein that is 99.2% identical to the human, differing at only 3 amino acids. The gene (M17S1) was mapped to mouse chromosome 11, high-lighting the conserved linkage synteny existing between human chromosome 17 and mouse chromosome 11. Although the nude locus has been mapped to the same region of chromosome 11, no abnormalities in protein, mRNA, or cDNA or genomic sequences were detected in nude mice. However, both nude and control mice were found to have a second Esa mRNA transcript that conserves amino acid sequence and molecular weight. The mouse and human 5' and 3' untranslated sequences are conserved. Similar RNA folding patterns of the 5' untranslated region are predicted despite a 91-bp insertion in the mouse. These data suggest that both the function and the regulation of ESA protein are of importance and that Esa (M17S1) is not the nude locus gene. PMID:7557989

  2. Studies on vacuum evaporated PbS 1- xSe x thin films

    NASA Astrophysics Data System (ADS)

    Kumar, Sushil; Majeed Khan, M. A.; Khan, Shamshad A.; Husain, M.

    2004-02-01

    The narrow gap IV-VI semiconductors have been the subject of extensive research owing to their technological importance. The fabrication of devices with alloys of these compounds with detecting and lasing capabilities has been an important recent technological development. The high quality polycrystalline thin films of PbS 1- xSe x with variable composition (0⩽ x⩽1) have been deposited onto ultra clean glass substrates by vacuum evaporation technique. Asdeposited films were annealed in vacuum at 350 K. Structural, electrical and optical properties of PbS 1- xSe x thin films have been examined. The X-ray diffraction patterns were used to determine the sample quality, crystal structure and lattice parameter of the films. The dc conductivity and activation energy of the films were measured in the temperature range 300-380 K. The absorption coefficient and band gap of the films were determined by absorbance measurements in wavelength range 2500-5000 nm using FTIR spectrophotometer.

  3. Targeted Proteomics-Driven Computational Modeling of Macrophage S1P Chemosensing.

    PubMed

    Manes, Nathan P; Angermann, Bastian R; Koppenol-Raab, Marijke; An, Eunkyung; Sjoelund, Virginie H; Sun, Jing; Ishii, Masaru; Germain, Ronald N; Meier-Schellersheim, Martin; Nita-Lazar, Aleksandra

    2015-10-01

    Osteoclasts are monocyte-derived multinuclear cells that directly attach to and resorb bone. Sphingosine-1-phosphate (S1P)(1) regulates bone resorption by functioning as both a chemoattractant and chemorepellent of osteoclast precursors through two G-protein coupled receptors that antagonize each other in an S1P-concentration-dependent manner. To quantitatively explore the behavior of this chemosensing pathway, we applied targeted proteomics, transcriptomics, and rule-based pathway modeling using the Simmune toolset. RAW264.7 cells (a mouse monocyte/macrophage cell line) were used as model osteoclast precursors, RNA-seq was used to identify expressed target proteins, and selected reaction monitoring (SRM) mass spectrometry using internal peptide standards was used to perform absolute abundance measurements of pathway proteins. The resulting transcript and protein abundance values were strongly correlated. Measured protein abundance values, used as simulation input parameters, led to in silico pathway behavior matching in vitro measurements. Moreover, once model parameters were established, even simulated responses toward stimuli that were not used for parameterization were consistent with experimental findings. These findings demonstrate the feasibility and value of combining targeted mass spectrometry with pathway modeling for advancing biological insight. PMID:26199343

  4. SUPPLEMENTARY COMPARISON: Final report on supplementary comparison SADCMET.AUV.V-S1

    NASA Astrophysics Data System (ADS)

    Veldman, Ian; von Martens, Hans-Jürgen

    2004-01-01

    A supplementary comparison (SADC.AUV.V-S1) was organized to compare measurements of sinusoidal linear accelerations in the frequency range from 10 Hz to 10 kHz. In this bilateral comparison between the CSIR National Metrology Laboratory (CSIR-NML), South Africa and the Physikalisch-Technische Bundesanstalt (PTB), Germany both NMIs applied laser interferometry in compliance with method 3 of the international standard ISO 16063-11:1999. The complex charge sensitivity (magnitude and phase) of two different transfer standards (single-ended accelerometers) was measured at 37 frequencies. The results of the SADCMET.AUV.V-S1 are a set of comparison values and their uncertainties, and degrees of equivalence between these and between the two laboratories. From this complete set of results, six matrices of equivalence per accelerometer were selected and are demonstrated graphically. The deviations between the PTB and NML results were smaller than 0.6° and 2° for the phase shift measurements for the Endevco and Brüel & Kjær accelerometers respectively (37 measurement points each). Main text. To reach the main text of this paper, click on Final Report. The final report has been peer-reviewed and approved for publication by SADCMET, according to the provisions of the Mutual Recognition Arrangement (MRA).

  5. S1 domain-containing STF modulates plastid transcription and chloroplast biogenesis in Nicotiana benthamiana.

    PubMed

    Jeon, Young; Jung, Hyun Ju; Kang, Hunseung; Park, Youn-Il; Lee, Soon Hee; Pai, Hyun-Sook

    2012-01-01

    • In this study, we examined the biochemical and physiological functions of Nicotiana benthamiana S1 domain-containing Transcription-Stimulating Factor (STF) using virus-induced gene silencing (VIGS), cosuppression, and overexpression strategies. • STF : green fluorescent protein (GFP) fusion protein colocalized with sulfite reductase (SiR), a chloroplast nucleoid-associated protein also present in the stroma. Full-length STF and its S1 domain preferentially bound to RNA, probably in a sequence-nonspecific manner. • STF silencing by VIGS or cosuppression resulted in severe leaf yellowing caused by disrupted chloroplast development. STF deficiency significantly perturbed plastid-encoded multimeric RNA polymerase (PEP)-dependent transcript accumulation. Chloroplast transcription run-on assays revealed that the transcription rate of PEP-dependent plastid genes was reduced in the STF-silenced leaves. Conversely, the exogenously added recombinant STF protein increased the transcription rate, suggesting a direct role of STF in plastid transcription. Etiolated seedlings of STF cosuppression lines showed defects in the light-triggered transition from etioplasts to chloroplasts, accompanied by reduced light-induced expression of plastid-encoded genes. • These results suggest that STF plays a critical role as an auxiliary factor of the PEP transcription complex in the regulation of plastid transcription and chloroplast biogenesis in higher plants. PMID:22050604

  6. Epidermal surface antigen (MS17S1) is highly conserved between mouse and human

    SciTech Connect

    Cho, Y.J.; Chema, D.; Cho, M.

    1995-05-20

    A mouse monoclonal antibody ECS-1 raised to human keratinocytes detects a 35-kDa epidermal surface antigen (ESA) and causes keratinocyte dissociation in vitro. ECS-1 stains skin of 16-day mouse embryo and 8- to 9-week human fetus. Mouse Esa cDNA encodes a 379-amino-acid protein that is 99.2% identical to the human, differing at only 3 amino acids. The gene (M17S1) was mapped to mouse chromosome 11, highlighting the conserved linkage synteny existing between human chromosome 17 and mouse chromosome 11. Although the nude locus has been mapped to the same region of chromosome 11, no abnormalities in protein, mRNA, or cDNA or genomic sequences were detected in nude mice. However, both nude and control mice were found to have a second Esa mRNA transcript that conserves amino acid sequence and molecular weight. The mouse and human 5{prime} and 3{prime} untranslated sequences are conserved. Similar RNA folding patterns of the 5{prime} untranslated region are predicted despite a 91-bp insertion in the mouse. These data suggest that both the function and the regulation of ESA protein are of importance and that Esa (M17S1) is not the nude locus gene. 42 refs., 7 figs., 3 tabs.

  7. A second species of spinons in the S=1/2 Heisenberg antiferromagnet on kagome

    NASA Astrophysics Data System (ADS)

    Mellado, Paula; Hao, Zhihao; Tchernyshyov, Oleg

    2010-03-01

    The S=1/2 Heisenberg model on kagome can be viewed as an ensemble of spinons, fermionic quasiparticles with S=1/2 bound into small, heavy pairs whose binding energy sets the spin gap [1]. The apparent lack of a spin gap in real kagome magnets (e.g. herbertsmithite) may be associated with the Dzyaloshinskii-Moriya (DM) term D .(SixSj) in the Hamiltonian allowed by lattice symmetry. The DM term suppresses the spin gap and eventually induces long-range magnetic order [2]. A recent study [3] hints at the presence of an intermediate gapless phase without magnetic order. We propose that this phase arises as a result of condensation of a second spinon species (kinks). Here we study the motion of a single kink on the Husimi cactus, the analog of kagome in a hyperbolic plane. The kink is localized in the pure Heisenberg model and becomes mobile when D !=0. We calculate the one-particle density of states and the bandwidth. [1] Z. Hao and O. Tchernyshyov, Phys. Rev. Lett. 103, 187203 (2009). [2] O. C'epas et al., Phys. Rev. B 78, 140405 (2008). [3] I. Rousochatzakis et al., Phys. Rev. B 79, 214415 (2009).

  8. Isomerization, Perturbations, Calculations and the S_{1} State of C_{2}H_{2}

    NASA Astrophysics Data System (ADS)

    Baraban, J. H.; Changala, P. B.; Berk, J. R. P.; Field, R. W.; Stanton, J. F.; Merer, A. J.

    2013-06-01

    Preliminary analysis of the energy region of the cis-trans isomerization transition state on the S_{1} surface of C_{2}H_{2} has revealed novel patterns and surprising perturbations, including unusually large (and high-order) anharmonicities, as well as K-staggerings of several vibrational levels. These effects complicate the analysis considerably, and require new models and calculations to account for and predict features of the observed spectra. The ˜{A}-˜{X} spectrum of acetylene has been studied both experimentally and theoretically for almost a century, and this cycle of unexpected phenomena eliciting innovative responses is found throughout its history. Especially in the last ten years, progress in understanding the S_{1} state rovibrational level structure and cis-trans isomerization has been accelerated by combining the information available from both ab initio computation and spectroscopic observations. The resulting dialogue has then frequently suggested fruitful avenues for further experiments and calculations. Current challenges and recent results in understanding the cis-trans isomerization transition state region will be discussed in this context.

  9. Sphingosine 1-Phosphate (S1P) Induced Interleukin-8 (IL-8) Release Is Mediated by S1P Receptor 2 and Nuclear Factor κB in BEAS-2B Cells

    PubMed Central

    O’Sullivan, Michael J.; Hirota, Nobuaki; Martin, James G.

    2014-01-01

    The airway epithelium may release pro-inflammatory cytokines and chemokines in the asthmatic airway. Sphingosine 1-phosphate (S1P) is a bioactive lipid, increased in the airways of asthmatics, that may trigger the release of the potent neutrophil chemoattractant Interleukin-8 (IL-8) by epithelial cells. S1P is a ligand for 5 G protein-coupled receptors, S1PR1-5. We wished to explore the mechanisms of S1P induced IL-8 secretion with regard to the receptor(s) and downstream signaling events involved. Our results indicate that S1P induced IL-8 release is mediated by S1PR2 and the transcription factor NF-κB. Since the Epidermal Growth Factor Receptor (EGFR) and reactive oxygen species (ROS) have been implicated in IL-8 release in response to activation of other G protein-coupled receptors, we examined their importance in S1P induced IL-8 release and established that they are not involved. This study reveals S1PR2 and NF-κB as potential therapeutic targets in neutrophilic airway diseases such as severe asthma. PMID:24743449

  10. Immunogenicity and protective efficacy of recombinant S1 domain of the porcine epidemic diarrhea virus spike protein.

    PubMed

    Oh, Jongsuk; Lee, Kyung-Won; Choi, Hwan-Won; Lee, Changhee

    2014-11-01

    Porcine epidemic diarrhea virus (PEDV) is a highly contagious enteric pathogen of swine. Acute PEDV outbreaks have continually emerged in most swine-producing Asian countries and, recently, in the United States, causing significant economic losses in the pig industry. The spike (S) protein of PEDV is a type 1 transmembrane envelope glycoprotein and consists of the S1 and S2 domains, which are responsible for virus binding and fusion, respectively. Since the S1 domain is involved in a specific high-affinity interaction with the cellular receptor and induction of neutralizing antibody in the natural host, it is a primary target for the development of effective vaccines against PEDV. In this study, a codon-optimized PEDV S1 gene containing amino acid residues 25-738 was synthesized based on a multiple alignment of the S amino acid sequences of PEDV field isolates and used to establish a stable porcine cell line constitutively expressing the PEDV S1 protein. The purified recombinant S1 protein was found to mediate highly potent antibody responses in immunized rabbits. The antibodies strongly recognized the recombinant S1 protein from cell lysates and supernatants of S1-expressing cells, whereas they bound weakly to the authentic S protein of PEDV vaccine strain SM98-1. Furthermore, a serum neutralization test revealed that the rabbit antisera completely inhibit infection of the PEDV vaccine strain at a serum dilution of 1:16. We then tested the ability of vaccination with the recombinant S1 protein to protect piglets against PEDV. Late-term pregnant sows were inoculated intramuscularly with the purified S1 protein, and the outcome was investigated in passively immunized suckling piglets after a virulent PEDV challenge. The results showed that vaccination with S1 protein efficiently protected neonatal piglets against PEDV. Our data suggest that the recombinant S1 protein shows potential as an effective and safe subunit vaccine for PED prevention. PMID:25008896

  11. Far-UV observations of comet C/2012 S1 (ISON) with FORTIS

    NASA Astrophysics Data System (ADS)

    McCandliss, Stephan R.; Feldman, Paul D.; Weaver, Harold A.; Fleming, Brian; Redwine, Keith; Li, Mary J.; Kutyrev, Alexander; Moseley, Samuel H.

    2015-01-01

    Far-UV imagery and objective grating spectroscopy of comet C/2012 S1 (ISON) were acquired from NASA sounding rocket 36.296 UG, launched on 20 November 2013 at 04:40 MST (20.48 Nov 2013 UT), 8.32 days pre-perihelion, from the White Sands Missile Range, NM. The comet was 0.1° below ground horizon, 0.44 AU from the Sun, 0.86 AU from the Earth, and at a solar elongation of 26.3°. The payload reached an apogee of 279 km and the total time pointed at the comet was 353 s. At the time of launch ISON was undergoing a factor of 5 increase in water production rate, going from 3.5e29 to 19.6e29 molecules s-1between 19.6 and 21.6 Nov (Combi et al. 2014), marking what is thought to be a final fragmentation event (Sekanina & Kracht 2014). Our instrument, a wide-field multi-object spectro-telescope called FORTIS (Far-UV Off Rowland-circle Telescope for Imaging and Spectroscopy), observed Lyα emissions in an objective grating mode through an open microshutter array, developed at the Goddard Space Flight Center, over a (1/2°)2 field-of-view. After accounting for slit losses and deadtime corrections we find a preliminary lower limit to the Lyα surface brightness of ~ 400 kilorayleighs, yielding a hydrogen production rate of QH ~ 5e29 atoms s-1, in reasonable agreement with the Combi result. We also acquired a broadband image of the comet in the 1280 to 1900 Å bandpass. This image shows a drop in count rate proportional to altitude caused by increased absorption of cometary emissions by terrestrial O2 located in the lower thermosphere. O2 absorption acts as a selective time dependent filter that attenuates cometary emissions from different atomic and molecular species at different rates during descent. Preliminary analysis suggests that the dominant species in a (1e5 km)2 nuclear region is neutral carbon. The radial profile in comparison to a Haser model suggests that the C parent molecule had a lifetime (at 1 AU) ~ 105 s; much shorter than the expected lifetime of CO. We

  12. Complete Genome Sequence of a Marine Bacterium, Pseudomonas pseudoalcaligenes Strain S1, with High Mercury Resistance and Bioaccumulation Capacity.

    PubMed

    Liu, Bing; Bian, Chao; Huang, Huiwei; Yin, Zhiwei; Shi, Qiong; Deng, Xu

    2016-01-01

    Pseudomonas pseudoalcaligenes S1, a marine bacterium, exhibited strong resistance to a high concentration of Hg(2+) and remarkable Hg(2+) bioaccumulation capacity. Here, we report the 6.9-Mb genome sequence of P. pseudoalcaligenes S1, which may help clarify its phylogenetic status and provide further understanding of the mechanisms of mercury bioremediation in a marine environment. PMID:27198018

  13. Activities of complete and truncated forms of pertussis toxin subunits S1 and S2 synthesized by Escherichia coli.

    PubMed Central

    Locht, C; Cieplak, W; Marchitto, K S; Sato, H; Keith, J M

    1987-01-01

    The genes encoding the S1 and S2 subunits of pertussis toxin were expressed in Escherichia coli under lac operon transcription and translation control with pUC8 and pUC18 as the expression vectors. Various versions of the subunits were detected with anti-S1 or anti-S2 monoclonal antibodies. Recombinant S1, but not S2, subunit contained the enzymatic NAD-glycohydrolase and NAD:Gi ADP-ribosyltransferase activities. Both activities were also expressed by a truncated version of the S1 subunit in which the 48 carboxy-terminal amino acid residues, including a predicted Rossman structure and one of the two cysteines, had been deleted. The epitope for an anti-S2 monoclonal antibody was localized to the N-terminal 40-amino-acid region of the S2 subunit. Both the S1 and S2 subunits expressed in E. coli reacted with human hyperimmune serum. The full length and the truncated recombinant S1 subunit also reacted in Western blots with a neutralizing and protective monoclonal anti-S1 antibody. The different versions of S1 and S2 subunits expressed in E. coli are useful for mapping active sites, epitopes, and regions that interact with receptors or the other subunits in the holotoxin. These recombinant subunits will also facilitate the development of a safer, new-generation vaccine against whooping cough. Images PMID:3117686

  14. The Sphingolipid Receptor S1PR2 Is a Receptor for Nogo-A Repressing Synaptic Plasticity

    PubMed Central

    Arzt, Michael E.; Weinmann, Oliver; Obermair, Franz J.; Pernet, Vincent; Zagrebelsky, Marta; Delekate, Andrea; Iobbi, Cristina; Zemmar, Ajmal; Ristic, Zorica; Gullo, Miriam; Spies, Peter; Dodd, Dana; Gygax, Daniel; Korte, Martin; Schwab, Martin E.

    2014-01-01

    Nogo-A is a membrane protein of the central nervous system (CNS) restricting neurite growth and synaptic plasticity via two extracellular domains: Nogo-66 and Nogo-A-Δ20. Receptors transducing Nogo-A-Δ20 signaling remained elusive so far. Here we identify the G protein-coupled receptor (GPCR) sphingosine 1-phosphate receptor 2 (S1PR2) as a Nogo-A-Δ20-specific receptor. Nogo-A-Δ20 binds S1PR2 on sites distinct from the pocket of the sphingolipid sphingosine 1-phosphate (S1P) and signals via the G protein G13, the Rho GEF LARG, and RhoA. Deleting or blocking S1PR2 counteracts Nogo-A-Δ20- and myelin-mediated inhibition of neurite outgrowth and cell spreading. Blockade of S1PR2 strongly enhances long-term potentiation (LTP) in the hippocampus of wild-type but not Nogo-A−/− mice, indicating a repressor function of the Nogo-A/S1PR2 axis in synaptic plasticity. A similar increase in LTP was also observed in the motor cortex after S1PR2 blockade. We propose a novel signaling model in which a GPCR functions as a receptor for two structurally unrelated ligands, a membrane protein and a sphingolipid. Elucidating Nogo-A/S1PR2 signaling platforms will provide new insights into regulation of synaptic plasticity. PMID:24453941

  15. The Occurrence of Type S1A Serine Proteases in Sponge and Jellyfish

    NASA Technical Reports Server (NTRS)

    Rojas, Ana; Doolittle, Russell F.

    2003-01-01

    Although serine proteases are found in all kinds of cellular organisms and many viruses, the classic "chymotrypsin family" (Group S1A by th e 1998 Barrett nomenclature) has an unusual phylogenetic distribution , being especially common in animals, entirely absent from plants and protists, and rare among fungi. The distribution in Bacteria is larg ely restricted to the genus Streptomyces, although a few isolated occ urrences in other bacteria have been reported. The family may be enti rely absent from Archaea. Although more than a thousand sequences have been reported for enzymes of this type from animals, none of them ha ve been from early diverging phyla like Porifera or Cnidaria, We now report the existence of Group SlA serine proteases in a sponge (phylu m Porifera) and a jellyfish (phylum Cnidaria), making it safe to conc lude that all animal groups possess these enzymes.

  16. Distribution of Exchange Energy in a Bond-alternating S=1 Quantum Spin Chain

    SciTech Connect

    Zheludev, Andrey I; Masuda, Takatsugu; Sales, Brian C; Mandrus, David; Papenbrock, Thomas F; Barnes, Ted {F E }; Park, S.

    2004-01-01

    The quasi-one-dimensional bond-alternating S=1 quantum antiferromagnet [Ni(N,N'-bis(3aminopropyl)propane-1,3-diamine({mu}-NO{sub 2})]ClO{sub 4} (NTENP) is studied by single-crystal inelastic neutron scattering. Parameters of the measured dispersion relation for magnetic excitations are compared to existing numerical results and used to determine the magnitude of bond-strength alternation. The measured neutron-scattering intensities are also analyzed, using the first-moment sum rules for the magnetic dynamic structure factor, to directly determine the modulation of ground-state exchange energies. These independently determined modulation parameters characterize the level of spin dimerization in NTENP. First-principles density-matrix renormalization-group calculations are used to study the relation between these two quantities.

  17. Classifying magnetic and superfluid equilibrium states in magnets with the spin s = 1

    NASA Astrophysics Data System (ADS)

    Kovalevskii, M. Yu.

    2016-03-01

    Based on the method of quasiaverages, we classify magnetic and superfluid equilibrium states in magnets with the spin s = 1. Under certain simplifications, assumptions about the residual symmetry of degenerate states and the transformation properties of order parameter operators under transformations generated by additive integrals of motions lead to linear algebraic equations for a classification of the equilibrium means of the order parameters. We consider different cases of the magnetic SO(3) or SU(3) symmetry breaking and obtain solutions for the vector and tensor order parameters for particular forms of the parameters of the residual symmetry generators. We study the equilibriums of magnets with simultaneously broken phase and magnetic symmetries. We find solutions of the classification equations for superfluid equilibrium states and establish relations between the parameters of the residual symmetry generator that allow the thermodynamic coexistence of nonzero equilibrium means of the order parameters.

  18. Clinical and morphological study of calf enlargement following S-1 radiculopathy.

    PubMed

    Nascimento, O J; De Freitas, M R; Hahn, M D; Araújo, A Q

    1992-09-01

    Calf enlargement following sciatica is a rare condition. It is reported the case of a 28-year-old woman who complained of repeated episodes of lower back pain radiating into the left buttock and foot. One year after the beginning of her symptoms, she noticed enlargement of her left calf. X-ray studies disclosed L5-S1 disk degeneration. EMG showed muscle denervation with normal motor conduction velocity. Open biopsies of the gastrocnemius muscles were performed. The left gastrocnemius muscle showed hypertrophic type 2 fibers in comparison with the right gastrocnemius. Electron microscopy showed mildly increased number of mitochondria in these fibers. A satisfactory explanation for denervation hypertrophy has yet to be provided. PMID:1308420

  19. Early changes in shoot transcriptome of rice in response to Rhodotorula mucilaginosa JGTA-S1

    PubMed Central

    Saha, Chinmay; Seal, Anindita

    2015-01-01

    Yeasts of Rhodotorula genus have been reported to show endophytic colonization in different plants. Some of the Rhodotorula species are found to exhibit plant growth promoting activities and also have been reported to protect plants against invading pathogens. A yeast strain closely related to Rhodotorula mucilaginosa was isolated from the endosphere of Typha angustifolia collected from a Uranium mine. A microarray analysis was performed to investigate the early changes in rice shoot transcripts in response to this yeast (R. mucilaginosa JGTA-S1). Transcriptional changes were monitored in 6 h and 24 h treated rice plant shoots as compared to 0 h control. The microarray data has been submitted to the NCBI GEO repository under the accession number of GSE64321. PMID:26697384

  20. IMAGING COMET ISON C/2012 S1 IN THE INNER CORONA AT PERIHELION

    SciTech Connect

    Druckmüller, Miloslav; Habbal, Shadia Rifai; Aniol, Peter; Ding, Adalbert; Morgan, Huw

    2014-04-01

    Much anticipation and speculation were building around comet ISON, or C/2012 S1, discovered on 2012 September 21 by the International Scientific Optical Network telescope in Russia, and bound for the Sun on 2013 November 28, with a closest heliocentric approach distance of 2.7 R {sub ☉}. Here we present the first white light image of the comet's trail through the inner corona. The image was taken with a wide field Lyot-type coronagraph from the Mees Observatory on Haleakala at 19:12 UT, past its perihelion passage at 18:45 UT. The perfect match between the comet's trail captured in the inner corona and the trail that had persisted across the field of view of 2-6 R {sub ☉} of the Solar and Heliospheric Observatory Large Angle and Spectrometric Coronagraph Experiment/C2 coronagraph at 19:12 UT demonstrates that the comet survived its perihelion passage.

  1. Quantum size effects on CdTexS1 - x semiconductor-doped glass

    NASA Astrophysics Data System (ADS)

    Medeiros Neto, J. A.; Barbosa, L. C.; Cesar, C. L.; Alves, O. L.; Galembeck, F.

    1991-11-01

    We present experimental evidences of quantum confinement in borosilicate glasses with a new microcrystallite CdTexS1-x semiconductor. The microcrystallite sizes are controlled by the heat-treatment time and temperature. Transmission electron microscopy measurements show the microcrystallites average diameters near 55 Å for the sample treated for the longest time. We observe a red shift from 570 to 640 nm in the absorption and photoluminescence spectra as the size increases. These shifts agree with the expected quantum-confined energies, varying from 0.80 to 0.60 eV. The absorption spectra also show a second feature which can be assigned to the second quantum-confined transition.

  2. Color coherence in p pbar collisions at squareroot s = 1.8 TeV

    SciTech Connect

    Abachi, S.

    1996-09-01

    We report on two preliminary studies of color coherence effects on {ital p}{ital {anti p}} collisions based on data collected by the D{null} detector during the 1992-1993 and 1994-1995 runs at the Fermilab Tevatron collider at a center of mass energy {radical}s = 1. 8 TeV. Demonstration of initial-to-final state color interference effects is done in a higher energy region by measuring spatial correlations between the softer third jet and the second leading- {ital E}{sub {ital T}} jet in multi-jet events and in a lower energy regime by examining particle distribution patterns in W+Jet events. The data are compared to Monte Carlo simulations with different color coherence implementations and the predictions of an NLO parton level calculation.

  3. Minimally Invasive Approach For Extraforaminal Synovial Cyst L5-S1

    PubMed Central

    Torres Campa-Santamarina, Jose; Towne, Sara; Alimi, Marjan; Härtl, Roger

    2015-01-01

    Symptoms from synovial cysts are produced by neural compression in the spinal canal or the foramen. Few cases of extraforaminal synovial cyst have been published in the literature. This is a case report of a 65-year-old female who presented with a three-month history of sciatic pain and no relief with conservative treatment. MRI showed a left-sided extraforaminal synovial cyst at L5-S1 with compression of the L5 nerve root at the lateral portion of the foramen. Minimally invasive surgery for resection was performed using an extraforaminal tubular microscopic endoscopy-assisted approach. The patient improved clinically and remained symptom-free for the entire follow-up of 30 months. PMID:26623217

  4. Magnetic studies of S=1/2 kagom'e lattice single crystals

    NASA Astrophysics Data System (ADS)

    Han, Tianheng; Chu, Shaoyan; Takano, Yasu; Rodriguez-Rivera, Jose; Broholm, Collin; Nocera, Daniel; Lee, Young

    2012-02-01

    Herbertsmithite ZnCu3(OH)6Cl2--one of the most promising quantum spin liquid candidates--presents a promising system for studies of frustrated magnetism on an S=1/2 kagom'e lattice. Following our recent success in crystal growth, we have measured anisotropies in the magnetic susceptibility and specific heat. The implication on the Hamiltonian will be discussed. Specific heat has been measured at dilution fridge temperatures up to 18 T on a single crystal sample which gives further information on the low temperature phases. In addition, inelastic neutron scattering has been performed and the broad continuum observed is consistent with deconfined 2D spinons which lends further support of herbertsmithite's quantum spin liquid candidacy.

  5. Technical evaluation report for the demonstration of radio frequency soil decontamination at Site S-1

    SciTech Connect

    Lyon, C.R.; Blanchard, C.F.; Whitt, L.H.

    1995-04-01

    The Air Force`s Armstrong Laboratory at Tyndall Air Force Base, Florida, has supported the research and development of Radio Frequency Soil Decontamination. Radio frequency soil decontamination is essentially a heat-assisted soil vapor extraction process. Site S-1 at Kelly Air Force Base, San Antonio, Texas, was selected for the demonstration of two patented techniques. The site is a former sump that collected spills and surface run-off from a waste petroleum, oils, and lubricants and solvent storage and transfer area. In 1993, a technique developed by the IIT Research Institute using an array of electrodes placed in the soil was demonstrated. In 1994, a technique developed by KAI Technologies, Inc. using a single applicator placed in a vertical borehole was demonstrated. Approximately 120 tons of soil were heated during each demonstration to a temperature of about 150 degrees Celsius.

  6. Symplectic {S}^{1} × N^3 , subgroup separability, and vanishing Thurston norm

    NASA Astrophysics Data System (ADS)

    Friedl, Stefan; Vidussi, Stefano

    2008-04-01

    Let N be a closed, oriented 3 -manifold. A folklore conjecture states that S^{1} × N admits a symplectic structure if and only if N admits a fibration over the circle. We will prove this conjecture in the case when N is irreducible and its fundamental group satisfies appropriate subgroup separability conditions. This statement includes 3 -manifolds with vanishing Thurston norm, graph manifolds and 3 -manifolds with surface subgroup separability (a condition satisfied conjecturally by all hyperbolic 3 -manifolds). Our result covers, in particular, the case of 0-framed surgeries along knots of genus one. The statement follows from the proof that twisted Alexander polynomials decide fiberability for all the 3 -manifolds listed above. As a corollary, it follows that twisted Alexander polynomials decide if a knot of genus one is fibered.

  7. Doubly degenerate entanglement spectrum and entanglement plateau in the S=1 bond-alternating chain

    NASA Astrophysics Data System (ADS)

    Deng, Xiao-Yan; Dou, Jun-Ya; Liu, Guang-Hua

    2015-12-01

    Quantum entanglement, entanglement spectrum, magnetization, and ground-state energy of the S=1 bond-alternating antiferromagnetic Heisenberg chain under magnetic field are investigated by the infinite time-evolving block decimation (iTEBD) method. Bipartite entanglement and entanglement spectrum are found to be capable of describing all the quantum phase transitions (QPTs). A rich ground-state phase diagram, which comprises of five different phases, i.e., a singlet-dimer phase, a Haldane phase, a Tomonaga-Luttinger liquid (TLL) phase, a 1/2 plateau phase, and a saturated ferromagnetic phase, is determined. It is interesting that, with the appearance of magnetization plateaus, entanglement plateaus are observed simultaneously. In the Haldane phase, doubly degenerate entanglement spectra on both even and odd bonds are observed. However, in the 1/2 plateau phase, only the entanglement spectra on the even bonds are found to be doubly degenerated.

  8. Magnetic entropy change of itinerant electron metamagnetic system Co(S1-xSex)2

    NASA Astrophysics Data System (ADS)

    Wada, H.; Mitsuda, A.; Tanaka, K.

    2006-12-01

    The magnetic entropy change, ΔSM , of Co(S1-xSex)2 has been studied for 0≤x≤0.11 . Compounds with 0.03≤x≤0.11 undergo a first-order magnetic transition and exhibit itinerant electron metamagnetism (IEM) just above the Curie temperature. We observed that the peak value of ΔSM shows a maximum at around x=0.07 . The results are compared with the theoretically calculated results based on the spin fluctuation theory of IEM reported by Yamada and Goto. It is found that the experimental results are well described by the theoretical calculations. The origin of the peak of ΔSM is discussed from the thermodynamical point of view.

  9. Progress towards measuring the 2S1 / 2 to 2P1 / 2 interval in hydrogen

    NASA Astrophysics Data System (ADS)

    Vutha, A. C.; Bezginov, N.; Ferchichi, I.; Hessels, E. A.

    2015-05-01

    There is a large discrepancy between the CODATA value for the proton charge radius, and its determinations from muonic hydrogen measurements. This discrepancy is referred to as the proton radius puzzle. Improved measurements on atomic hydrogen can elucidate the origins of this discrepancy. We have constructed an experiment to measure the Lamb shift (n = 2 ,S1 / 2 -->P1 / 2) in a fast beam of atomic hydrogen. Using a novel separated-oscillatory-fields method and high signal-to-noise ratio detection, we can measure the center of this transition with a statistical uncertainty approaching 10-5 of its natural linewidth. We report on our studies of systematic effects, and on our progress towards a new measurement of the proton charge radius. We acknowledge funding from NSERC, CFI, CRC, ORF, and NIST.

  10. Preliminary Geologic Mapping of the Ac-S-1 Hemisphere of Ceres from NASA's Dawn Mission

    NASA Astrophysics Data System (ADS)

    Mest, S. C.; Williams, D. A.; Buczkowski, D. L.; Scully, J. E. C.; Crown, D. A.; Yingst, R. A.; Jaumann, R.; Russell, C. T.; Raymond, C. A.

    2015-10-01

    NASA's Dawn spacecraft [1], launched in September 2007, spent ~1 year (2011-2012) investigating Vesta and recently (March 6, 2015) arrived at dwarf planet Ceres. The first images of Ceres' surface were acquired by Dawn's Framing Camera (FC) [2] as it made optical navigation and rotation characterization observations during the Approach phase. The Dawn Science Team will conduct a geological mapping campaign at Ceres during the Nominal Mission, which will include iterative mapping using data obtained during each orbital phase. Iterative geologic mapping was previously successfully conducted during Dawn's mission to Vesta [3,4]. This abstract describes the preliminary geologic mapping results for quadrangle Ac-S-1 (55-90°N, 0-360°E), the northern hemisphere of Ceres.

  11. Picosecond transient gratings in CdS1- xSex mixed crystals

    NASA Astrophysics Data System (ADS)

    Dörnfeld, C.; Noll, G.; Schwab, H.; Hvam, J. M.; Weber, Ch.; Renner, R.; Göbel, E. O.; Reznitsky, A.; Lyssenko, V.; Pendjur, S. A.; Talensky, O. N.; Klingshirn, C.

    1990-04-01

    We performed transient grating experiments to study various relaxation processes of localized excitons in CdS1 xSex mixed crystals. At low temperatures we observe a strong nonlinear response, spectrally in the localized states. We measured the phase relaxation time of localized excitons with a correlation technique. At low excitation levels we found long phase relaxation times of 75 ps. In a three beam configuration of a transient grating experiment we investigated the recombination as well as the diffusion of excitons within the localized states. We observed a reduced mobility compared to the mobility of free excitons in the pure compounds and found diffusion coefficients D < 2 cm2/ s.

  12. Optical and Phonon Characterization of Ternary CdSe x S1- x Alloy Quantum Dots

    NASA Astrophysics Data System (ADS)

    Thi, L. A.; Cong, N. D.; Dang, N. T.; Nghia, N. X.; Quang, V. X.

    2016-05-01

    Ternary CdSe x S1- x alloy quantum dots (QDs) were synthesized using a wet chemical method. Their morphology, particle size, structural, optical, and vibrational properties were investigated using transmission electron microscopy, x-ray diffraction, UV-Vis, fluorescence and Raman spectroscopy, respectively. The optical and vibrational properties of the QDs can be controlled by adjusting the Se/S molar ratio. The absorption and emission peaks shift to a longer wavelength range when increasing the Se content. The presence of two CdSe-like and CdS-like longitudinal optical phonon modes was observed. The dependencies of the optical and phonon modes on the Se content are discussed in detail.

  13. O/S-1/ interactions - The product channels. [collisional electron quenching and chemical reaction pathway frequencies

    NASA Technical Reports Server (NTRS)

    Slanger, T. G.; Black, G.

    1978-01-01

    The first measurements are reported of the reaction pathways for the interaction between oxygen atoms in the 4.19 eV S-1 state, and four molecules, N2O, CO2, H2O, and NO. Distinction is made between three possible paths - quenching to O(D-1), quenching to O(P-3), and chemical reaction. With N2O, the most reasonable interpretation of the data indicates that there no reaction, in sharp contrast with the interaction between O(D-1) and N2O, which proceeds entirely by reaction. Similarly, there is no reaction with CO2. With H2O, the reactive pathway is the dominant one, although electronic quenching is not negligible. With NO, O(D-1) is the preferred product.

  14. Disorder-induced phases in the S=1 antiferromagnetic Heisenberg chain

    NASA Astrophysics Data System (ADS)

    Lajkó, Péter; Carlon, Enrico; Rieger, Heiko; Iglói, Ferenc

    2005-09-01

    We use extensive density matrix renormalization group (DMRG) calculations to explore the phase diagram of the random S=1 antiferromagnetic Heisenberg chain with a power-law distribution of the exchange couplings. We use open chains and monitor the lowest gaps, the end-to-end correlation function and the string order parameter. For this distribution at weak disorder, the system is in the gapless Haldane phase with a disorder dependent dynamical exponent, z , and z=1 signals the border between the nonsingular and singular regions of the local susceptibility. For strong enough disorder, which approximately corresponds to a uniform distribution, a transition into the random singlet phase is detected, at which the string order parameter as well as the average end-to-end correlation function are vanishing and at the same time the dynamical exponent is divergent. Singularities of physical quantities are found to be somewhat different in the random singlet phase and in the critical point.

  15. The Case for a Hubble Constant of 30 km s-1 Mpc-1.

    PubMed

    Bartlett, J G; Blanchard, A; Silk, J; Turner, M S

    1995-02-17

    Although recent determinations of the distance to the Virgo cluster based on Cepheid variable stars represent an important step in pinning down the Hubble constant, after 65 years a definitive determination of the Hubble constant still eludes cosmologists. At present, most of the observational determinations place the Hubble constant between 40 and 90 kilometers per second per megaparsec (km s(-1) Mpc(-1)). The case is made here for a Hubble constant that is even smaller than the lower bound of the accepted range on the basis of the great advantages, all theoretical in nature, of a Hubble constant of around 30 kilometers per second per megaparsec. Such a value for the Hubble cures all of the ills of the current theoretical orthodoxy, that is, a spatially flat universe composed predominantly of cold dark matter. PMID:17811436

  16. Lower Extremity Radicular Pain Caused by Entrapped Sigmoid Colon Between L5 and S1 Vertebrae

    PubMed Central

    Ko, Sanghyung; Park, Noh Kyoung; Cho, Kyoung Jin; Baek, Jung Hyun; Lim, Jeong-Wook; Choi, Dongjin

    2015-01-01

    Intestinal entrapment between two vertebral bodies is very rare. In all previous cases, it occurred by major trauma. However, the bowel entrapment between two vertebral bodies without trauma has never been reported, not to mention as the cause of lower extremity radicular pain. We describe the case of an 82-year-old female patient with right lower extremity radicular pain without recent trauma history. The patient was diagnosed sigmoid colon entrapment between the L5 and S1 vertebrae by lumbar spinal computerized tomography and magnetic resonance imaging, and showed improvement in radicular pain after manual reduction of interpositioned colon during surgery. Intestinal entrapment between two vertebrae without trauma is caused by degenerative and vacuum changes of the intervertebral disc combined with the anterior longitudinal ligament injury. PMID:26619145

  17. Gauged D=7 supergravity on the S1/Z2 orbifold

    NASA Astrophysics Data System (ADS)

    Avramis, Spyros D.; Kehagias, Alex

    2005-03-01

    We construct the most general couplings of a bulk seven-dimensional Yang-Mills-Einstein N =2 supergravity with a boundary six-dimensional chiral N =(0, 1) theory of vectors and charged hypermultiplets. The boundary consists of two brane worlds sitting at the fixed points of an S1/ Z2 compactification of the seven-dimensional bulk supergravity. The resulting 6D massless spectrum surviving the orbifold projection is anomalous. By introducing boundary fields at the orbifold fixed points, we show that all anomalies are canceled by a Green-Schwarz mechanism. In addition, all couplings of the boundary fields to the bulk are completely specified by supersymmetry. We emphasize that there is no bulk Chern-Simons term to cancel the anomalies. The latter is traded for a Green-Schwarz term which emerges in the boundary theory after a duality transformation implemented to construct the bulk supergravity.

  18. Phase diagram of S= 1 /2 two-leg XXZ spin-ladder systems

    NASA Astrophysics Data System (ADS)

    Hijii, Keigo; Kitazawa, Atsuhiro; Nomura, Kiyohide

    2005-07-01

    We investigate the ground-state phase diagram of the S=(1)/(2) two-leg XXZ spin-ladder system with an isotropic interchain coupling. In this model, there is the Berezinskii-Kosterlitz-Thouless transition which occurs at the XY -Haldane and XY -rung singlet phase boundaries. It was difficult to determine the transition line using traditional methods. We overcome this difficulty using the level spectroscopy method combined with the twisted boundary condition method, and we check the consistency. We find out that the phase boundary between XY phase and Haldane phase lies on Δ=0 line. And we show that there exist two different XY phases, which we can distinguish investigating a XX correlation function.

  19. Results from the worldwide coma morphology campaign for comet ISON (C/2012 S1)

    NASA Astrophysics Data System (ADS)

    Samarasinha, Nalin H.; Mueller, Beatrice E. A.; Knight, Matthew M.; Farnham, Tony L.; Briol, John; Brosch, Noah; Caruso, John; Gao, Xing; Gomez, Edward; Lister, Tim; Hergenrother, Carl; Hoban, Susan; Prouty, Roy; Holloway, Mike; Howes, Nick; Guido, Ernesto; Hui, Man-To; Jones, Joseph H.; Penland, Tyler B.; Thomas, Samuel R.; Wyrosdick, Jim; Kiselev, Nikolai; Ivanova, Aleksandra V.; Kaye, Thomas G.; Eluo, Jean-Baptist Kikwaya; Lau, Betty P. S.; Lin, Zhong-Yi; Martin, José Luis; Moskvitin, Alexander S.; Nicolini, Martino; Ottum, Brian D.; Pruzenski, Chris; Vogel, David C.; Kellett, Leo; Rapson, Valerie; Schmid, Joel; Doyle, Brandon; Dimino, Frank; Carlino, Stephanie; Safonova, Margarita; Murthy, Jayant; Sutaria, Firoza; Schleicher, David G.; Snodgrass, Colin; Tezcan, Cihan T.; Yorukoglu, Onur; Trowbridge, David; Whitmer, Dennis; Ye, Quan-Zhi

    2015-12-01

    We present the results of a global coma morphology campaign for comet C/2012 S1 (ISON), which was organized to involve both professional and amateur observers. In response to the campaign, many hundreds of images, from nearly two dozen groups were collected. Images were taken primarily in the continuum, which help to characterize the behavior of dust in the coma of comet ISON. The campaign received images from January 12 through November 22, 2013 (an interval over which the heliocentric distance decreased from 5.1 AU to 0.35 AU), allowing monitoring of the long-term evolution of coma morphology during comet ISON's pre-perihelion leg. Data were contributed by observers spread around the world, resulting in particularly good temporal coverage during November when comet ISON was brightest but its visibility was limited from any one location due to the small solar elongation. We analyze the northwestern sunward continuum coma feature observed in comet ISON during the first half of 2013, finding that it was likely present from at least February through May and did not show variations on diurnal time scales. From these images we constrain the grain velocities to ~10 m s-1, and we find that the grains spent 2-4 weeks in the sunward side prior to merging with the dust tail. We present a rationale for the lack of continuum coma features from September until mid-November 2013, determining that if the feature from the first half of 2013 was present, it was likely too small to be clearly detected. We also analyze the continuum coma morphology observed subsequent to the November 12 outburst, and constrain the first appearance of new features in the continuum to later than November 13.99 UT.

  20. Lipid receptor S1P₁ activation scheme concluded from microsecond all-atom molecular dynamics simulations.

    PubMed

    Yuan, Shuguang; Wu, Rongliang; Latek, Dorota; Trzaskowski, Bartosz; Filipek, Slawomir

    2013-01-01

    Sphingosine 1-phosphate (S1P) is a lysophospholipid mediator which activates G protein-coupled sphingosine 1-phosphate receptors and thus evokes a variety of cell and tissue responses including lymphocyte trafficking, endothelial development, integrity, and maturation. We performed five all-atom 700 ns molecular dynamics simulations of the sphingosine 1-phosphate receptor 1 (S1P₁) based on recently released crystal structure of that receptor with an antagonist. We found that the initial movements of amino acid residues occurred in the area of highly conserved W269⁶·⁴⁸ in TM6 which is close to the ligand binding location. Those residues located in the central part of the receptor and adjacent to kinks of TM helices comprise of a transmission switch. Side chains movements of those residues were coupled to the movements of water molecules inside the receptor which helped in the gradual opening of intracellular part of the receptor. The most stable parts of the protein were helices TM1 and TM2, while the largest movement was observed for TM7, possibly due to the short intracellular part starting with a helix kink at P⁷·⁵⁰, which might be the first helix to move at the intracellular side. We show for the first time the detailed view of the concerted action of the transmission switch and Trp (W⁶·⁴⁸) rotamer toggle switch leading to redirection of water molecules flow in the central part of the receptor. That event is a prerequisite for subsequent changes in intracellular part of the receptor involving water influx and opening of the receptor structure. PMID:24098103

  1. Spectroscopic study on deuterated benzenes. III. Vibronic structure and dynamics in the S(1) state.

    PubMed

    Kunishige, Sachi; Katori, Toshiharu; Kawabata, Megumi; Yamanaka, Takaya; Baba, Masaaki

    2015-12-28

    We observed the fluorescence excitation spectra and mass-selected resonance enhanced multiphoton ionization (REMPI) excitation spectra for the 6(0)(1), 6(0)(1)1(0)(1), and 6(0)(1)1(0)(2) bands of the S1←S0 transition of jet-cooled deuterated benzene and assigned the vibronic bands of C6D6 and C6HD5. The 6(0)(1)1(0)(n) (n = 0, 1, 2) and 0(0)(0) transition energies were found to be dependent only on the number of D atoms (ND), which was reflected by the zero-point energy of each H/D isotopomer. In some isotopomers some bands, such as those of out-of-plane vibrations mixed with 6(1)1(n), make the spectra complex. These included the 6(1)10(2)1(n) level or combination bands with ν12 which are allowed because of reduced molecular symmetry. From the lifetime measurements of each vibronic band, some enhancement of the nonradiative intramolecular vibrational redistribution (IVR) process was observed. It was also found that the threshold excess energy of "channel three" was higher than the 6(1)1(2) levels, which were similar for all the H/D isotopomers. We suggest that the channel three nonradiative process could be caused mainly by in-plane processes such as IVR and internal conversion at the high vibrational levels in the S1 state of benzene, although the out-of-plane vibrations might contribute to some degree. PMID:26723668

  2. Variations in the Blood Phenytoin Levels during Long-Term Combined Treatment with S-1 and Phenytoin

    PubMed Central

    Negoro, Yutaka; Higashi, Takashi; Matsuoka, Hiroaki; Watanabe, Kyohei; Igarashi, Toshiaki; Kayano, Yuichiro; Yano, Ryoichi; Nakamura, Toshiaki; Masada, Mikio

    2014-01-01

    Although combination therapy with the oral fluoropyrimidine anticancer drug S-1 and the anticonvulsant phenytoin (PHT) is known to increase blood levels of PHT and the risk of intoxication, reports on long-term monitoring of blood levels of PHT during combined S-1 and PHT treatment and a thorough understanding of their interaction are lacking. This report aims to describe interactive effects of S-1 and PHT through long-term therapeutic drug monitoring of PHT. A 72-year-old male had been prescribed oral PHT (130 mg/day) for over 20 years and started receiving S-1 therapy (80 mg/day for 4 weeks, followed by a 2-week rest) as postoperative adjuvant chemotherapy for gastric cancer. The blood PHT level was continuously monitored. Prior to receiving S-1, the patient's blood PHT concentration was 6.0 μg/ml, but it increased during S-1 therapy, reaching 22.9 μg/ml on day 84 (during a rest period of second cycle S-1 therapy). After reducing his PHT dosage to 100 mg/day, it never reached toxic levels (4.0–10.4 μg/ml). It was difficult to keep blood PHT concentrations constant because of the time lag between the period of combined use of S-1 and PHT and the timing of manifestation and disappearance of the drug interaction. The DIPS probability scale indicated a highly probable interaction between S-1 and PHT. We conclude that, when S-1 and PHT are used concurrently, occurrence and disappearance time of their interaction need to be predicted to maintain an effective and safe PHT concentration. PMID:25606031

  3. XPS and electroluminescence studies on SrS 1- xSe x and ZnS 1- xSe x thin films deposited by atomic layer deposition technique

    NASA Astrophysics Data System (ADS)

    Ihanus, Jarkko; Lambers, Eric; Holloway, Paul H.; Ritala, Mikko; Leskelä, Markku

    2004-01-01

    SrS 1- xSe x and ZnS 1- xSe x thin films were deposited by the atomic layer deposition (ALD) technique using elemental selenium as the Se source, thus avoiding use of H 2Se or organometallic selenium compounds. X-ray diffraction (XRD) analysis showed that the films were solid solutions and X-ray photoelectron spectroscopy (XPS) data showed that the surface of both ZnS 1- xSe x and SrS 1- xSe x were covered with an oxide and carbon-containing contaminants from exposure to air. The oxidation of SrS 1- xSe x extended into the film and peak shifts from sulfate were found on the surface. Luminance measurements showed that emission intensity of the ZnS 1- xSe x:Mn alternating current thin film electroluminescent (ACTFEL) devices at fixed voltage was almost the same as that of the ZnS:Mn device, while emission intensity of the SrS 1- xSe x:Ce devices decreased markedly as compared to the SrS:Ce device. Emission colors of the devices were altered only slightly due to selenium addition.

  4. Increased mRNA Levels of Sphingosine Kinases and S1P Lyase and Reduced Levels of S1P Were Observed in Hepatocellular Carcinoma in Association with Poorer Differentiation and Earlier Recurrence

    PubMed Central

    Uranbileg, Baasanjav; Ikeda, Hitoshi; Kurano, Makoto; Enooku, Kenichiro; Sato, Masaya; Saigusa, Daisuke; Aoki, Junken; Ishizawa, Takeaki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

    2016-01-01

    Although sphingosine 1-phosphate (S1P) has been reported to play an important role in cancer pathophysiology, little is known about S1P and hepatocellular carcinoma (HCC). To clarify the relationship between S1P and HCC, 77 patients with HCC who underwent surgical treatment were consecutively enrolled in this study. In addition, S1P and its metabolites were quantitated by LC-MS/MS. The mRNA levels of sphingosine kinases (SKs), which phosphorylate sphingosine to generate S1P, were increased in HCC tissues compared with adjacent non-HCC tissues. Higher mRNA levels of SKs in HCC were associated with poorer differentiation and microvascular invasion, whereas a higher level of SK2 mRNA was a risk factor for intra- and extra-hepatic recurrence. S1P levels, however, were unexpectedly reduced in HCC compared with non-HCC tissues, and increased mRNA levels of S1P lyase (SPL), which degrades S1P, were observed in HCC compared with non-HCC tissues. Higher SPL mRNA levels in HCC were associated with poorer differentiation. Finally, in HCC cell lines, inhibition of the expression of SKs or SPL by siRNA led to reduced proliferation, invasion and migration, whereas overexpression of SKs or SPL enhanced proliferation. In conclusion, increased SK and SPL mRNA expression along with reduced S1P levels were more commonly observed in HCC tissues compared with adjacent non-HCC tissues and were associated with poor differentiation and early recurrence. SPL as well as SKs may be therapeutic targets for HCC treatment. PMID:26886371

  5. Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation.

    PubMed

    Messias, Carolina V; Santana-Van-Vliet, Eliane; Lemos, Julia P; Moreira, Otacilio C; Cotta-de-Almeida, Vinicius; Savino, Wilson; Mendes-da-Cruz, Daniella Arêas

    2016-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in several physiological processes including cell migration and differentiation. S1P signaling is mediated through five G protein-coupled receptors (S1P1-S1P5). S1P1 is crucial to the exit of T-lymphocytes from the thymus and peripheral lymphoid organs through a gradient of S1P. We have previously observed that T-ALL and T-LBL blasts express S1P1. Herein we analyzed the role of S1P receptors in the migratory pattern of human T-cell neoplastic blasts. S1P-triggered cell migration was directly related to S1P1 expression. T-ALL blasts expressing low levels of S1P1 mRNA (HPB-ALL) did not migrate toward S1P, whereas those expressing higher levels of S1P1 (MOLT-4, JURKAT and CEM) did migrate. The S1P ligand induced T-ALL cells chemotaxis in concentrations up to 500 nM and induced fugetaxis in higher concentrations (1000-10000 nM) through interactions with S1P1. When S1P1 was specifically blocked by the W146 compound, S1P-induced migration at lower concentrations was reduced, whereas higher concentrations induced cell migration. Furthermore, we observed that S1P/S1P1 interactions induced ERK and AKT phosphorylation, and modulation of Rac1 activity. Responding T-ALL blasts also expressed S1P3 mRNA but blockage of this receptor did not modify migratory responses. Our results indicate that S1P is involved in the migration of T-ALL/LBL blasts, which is dependent on S1P1 expression. Moreover, S1P concentrations in the given microenvironment might induce dose-dependent chemotaxis or fugetaxis of T-ALL blasts. PMID:26824863

  6. Sphingosine-1-Phosphate Induces Dose-Dependent Chemotaxis or Fugetaxis of T-ALL Blasts through S1P1 Activation

    PubMed Central

    Messias, Carolina V.; Santana-Van-Vliet, Eliane; Lemos, Julia P.; Moreira, Otacilio C.; Cotta-de-Almeida, Vinicius; Savino, Wilson; Mendes-da-Cruz, Daniella Arêas

    2016-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid involved in several physiological processes including cell migration and differentiation. S1P signaling is mediated through five G protein-coupled receptors (S1P1-S1P5). S1P1 is crucial to the exit of T-lymphocytes from the thymus and peripheral lymphoid organs through a gradient of S1P. We have previously observed that T-ALL and T-LBL blasts express S1P1. Herein we analyzed the role of S1P receptors in the migratory pattern of human T-cell neoplastic blasts. S1P-triggered cell migration was directly related to S1P1 expression. T-ALL blasts expressing low levels of S1P1 mRNA (HPB-ALL) did not migrate toward S1P, whereas those expressing higher levels of S1P1 (MOLT-4, JURKAT and CEM) did migrate. The S1P ligand induced T-ALL cells chemotaxis in concentrations up to 500 nM and induced fugetaxis in higher concentrations (1000–10000 nM) through interactions with S1P1. When S1P1 was specifically blocked by the W146 compound, S1P-induced migration at lower concentrations was reduced, whereas higher concentrations induced cell migration. Furthermore, we observed that S1P/S1P1 interactions induced ERK and AKT phosphorylation, and modulation of Rac1 activity. Responding T-ALL blasts also expressed S1P3 mRNA but blockage of this receptor did not modify migratory responses. Our results indicate that S1P is involved in the migration of T-ALL/LBL blasts, which is dependent on S1P1 expression. Moreover, S1P concentrations in the given microenvironment might induce dose-dependent chemotaxis or fugetaxis of T-ALL blasts. PMID:26824863

  7. Dynamic Cross Talk between S1P and CXCL12 Regulates Hematopoietic Stem Cells Migration, Development and Bone Remodeling

    PubMed Central

    Golan, Karin; Kollet, Orit; Lapidot, Tsvee

    2013-01-01

    Hematopoietic stem cells (HSCs) are mostly retained in a quiescent non-motile mode in their bone marrow (BM) niches, shifting to a migratory cycling and differentiating state to replenish the blood with mature leukocytes on demand. The balance between the major chemo-attractants CXCL12, predominantly in the BM, and S1P, mainly in the blood, dynamically regulates HSC recruitment to the circulation versus their retention in the BM. During alarm situations, stress-signals induce a decrease in CXCL12 levels in the BM, while S1P levels are rapidly and transiently increased in the circulation, thus favoring mobilization of stem cells as part of host defense and repair mechanisms. Myeloid cytokines, including G-CSF, up-regulate S1P signaling in the BM via the PI3K pathway. Induced CXCL12 secretion from stromal cells via reactive oxygen species (ROS) generation and increased S1P1 expression and ROS signaling in HSCs, all facilitate mobilization. Bone turnover is also modulated by both CXCL12 and S1P, regulating the dynamic BM stromal microenvironment, osteoclasts and stem cell niches which all functionally express CXCL12 and S1P receptors. Overall, CXCL12 and S1P levels in the BM and circulation are synchronized to mutually control HSC motility, leukocyte production and osteoclast/osteoblast bone turnover during homeostasis and stress situations. PMID:24276423

  8. The impact of photon flight path on S1 pulse shape analysis in liquid xenon two-phase detectors

    NASA Astrophysics Data System (ADS)

    Moongweluwan, M.

    2016-02-01

    The LUX dark matter search experiment is a 350 kg dual-phase xenon time projection chamber located at the 4850 ft level of the Sanford Underground Research Facility in Lead, SD. The success of two-phase xenon detectors for dark matter searches relies on their ability to distinguish electron recoil (ER) background events from nuclear recoil (NR) signal events. Typically, the NR-ER discrimination is obtained from the ratio of the electroluminescence light (S2) to the prompt scintillation light (S1). Analysis of the S1 pulse shape is an additional discrimination technique that can be used to distinguish NR from ER. Pulse-shape NR-ER discrimination can be achieved based on the ratio of the de-excitation processes from singlet and triplet states that generate the S1. The NR S1 is dominated by the de-excitation process from singlet states with a time constant of about 3 ns while the ER S1 is dominated by the de-excitation process from triplet states with a time constant of about 24 ns. As the size of the detectors increases, the variation in the S1 photon flight path can become comparable to these decay constants, reducing the utility of pulse-shape analysis to separate NR from ER. The effect of path length variations in the LUX detector has been studied using the results of simulations and the impact on the S1 pulse shape analysis is discussed.

  9. GPCR cell signaling pathways mediating embryonic chick retinal growth cone collapse induced by LPA and S1P

    PubMed Central

    Fincher, Jarod; Whiteneck, Canaan; Birgbauer, Eric

    2014-01-01

    In the development of the nervous system, one of the critical aspects is the proper navigation of axons to their targets, the problem of axonal guidance. We are using the chick visual system as a model to investigate the role of the lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) as potential axon guidance cues. We show that both LPA and S1P cause specific, dose-dependent growth cone collapse of retinal neurons in vitro in the chick model system, with slight differences to mouse, but very similar to Xenopus. Because LPA and S1P receptors are GPCRs, we analyzed the intracellular signaling pathways using pharmacological inhibitors in chick retinal neurons. Blocking rho kinase (ROCK) prevented growth cone collapse by LPA and S1P, while blocking PLC or chelating calcium had no effect on growth cone collapse. Inhibiting Gi/o with pertussis toxin resulted in a partial reduction of growth cone collapse, both with LPA and S1P. Inhibition of p38 blocked growth cone collapse mediated by LPA but not S1P. Thus, in addition to the involvement of the G12/13-ROCK pathway, LPA and S1P induced collapse of chick retinal growth cones has a partial requirement for Gi/o. PMID:25138637

  10. The Pertussis Toxin S1 Subunit Is a Thermally Unstable Protein Susceptible to Degradation by the 20S Proteasome†

    PubMed Central

    Pande, Abhay H.; Moe, David; Jamnadas, Maneesha; Tatulian, Suren A.; Teter, Ken

    2008-01-01

    Pertussis toxin (PT) is an AB-type protein toxin that consists of a catalytic A subunit (PT S1) and an oligomeric, cell-binding B subunit. It belongs to a subset of AB toxins that move from the cell surface to the endoplasmic reticulum (ER) before A chain passage into the cytosol. Toxin translocation is thought to involve A chain unfolding in the ER and the quality control mechanism of ER-associated degradation (ERAD). The absence of lysine residues in PT S1 may allow the translocated toxin to avoid ubiquitin-dependent degradation by the 26S proteasome, which is the usual fate of exported ERAD substrates. As the conformation of PT S1 appears to play an important role in toxin translocation, we used biophysical and biochemical methods to examine the structural properties of PT S1. Our in vitro studies found that the isolated PT S1 subunit is a thermally unstable protein that can be degraded in a ubiquitin-independent fashion by the core 20S proteasome. The thermal denaturation of PT S1 was inhibited by its interaction with NAD, a donor molecule used by PT S1 for the ADP-ribosylation of target G proteins. These observations support a model of intoxication in which toxin translocation, degradation, and activity are all influenced by the heat-labile nature of the isolated toxin A chain. PMID:17105192

  11. Effect of oxidizable electrode material on resistive switching characteristics of ZnO(x)S(1-x) films.

    PubMed

    Cho, Kyoungah; Park, Sukhyung; Chung, Isaac; Kim, Sangsig

    2014-11-01

    We investigate the memory characteristics of ZnO(x(S(1-x) based resistive switching random access memory (ReRAM) devices with Al and Pt bottom electrodes (BEs). Both the ReRAM devices with Al and Pt BEs exhibit unipolar resistive switching behaviors, regardless of the materials of the BEs. The ratios of the high resistance state (HRS) to the low resistance state (LRS) of the Au/annealed ZnO(x)S(1-x)/Al and the Au/annealed ZnO(x)S(1-x)/Pt devices are more than 10(6) and 10(4), respectively. The HRS depends more significantly on the material of the BE than the LRS. The resistance in the HRS of the device with the Al BE is more stable in the endurance characteristics and higher in magnitude than that of the device with the Pt BE. For an anealed ZnO(x)S(1-x)/Al film, the oxygen signal in the auger depth profile shows the formation of an AIO(x) layer at the interface between the annealed ZnO(x)S(1-x) layer and the Al BE. The difference between the memory characteristics of the annealed ZnO(x)S(1-x) devices with the Al and Pt BEs is explained with the presence or absence of the oxidized layers formed in the interfaces between the annealed ZnO(x)S(1-x) films and the BEs. PMID:25958497

  12. Alpha S1-casein polymorphisms in camel (Camelus dromedarius) and descriptions of biological active peptides and allergenic epitopes.

    PubMed

    Erhardt, Georg; Shuiep, El Tahir Salih; Lisson, Maria; Weimann, Christina; Wang, Zhaoxin; El Zubeir, Ibtisam El Yas Mohamed; Pauciullo, Alfredo

    2016-06-01

    Milk samples of 193 camels (Camelus dromedarius) from different regions of Sudan were screened for casein variability by isoelectric focusing. Kappa-casein and beta-casein were monomorphic, whereas three protein patterns named αs1-casein A, C, and D were identified. The major allele A revealed frequencies of 0.79 (Lahaoi), 0.75 (Shanbali), 0.90 (Arabi Khali), and 0.88 (Arabi Gharbawi) in the different ecotypes. CSN1S1*C shows a single G > T nucleotide substitution in the exon 5, leading to a non-synonymous amino acid exchange (p.Glu30 > Asp30) in comparison to CSN1S1*A and D. At cDNA level, no further single nucleotide polymorphisms could be identified in CSN1S1* A, C, and D, whereas the variants CSN1S1*A and CSN1S1*C are characterized by missing of exon 18 compared to the already described CSN1S1*B, as consequence of DNA insertion of 11 bp at intron 17 which alter the pre-mRNA spliceosome machinery. A polymerase chain-restriction fragment length polymorphism method (PCR-RFLP) was established to type for G > T nucleotide substitution at genomic DNA level. The occurrence and differences of IgE-binding epitopes and bioactive peptides between αs1-casein A, C, and D after digestion were analyzed in silico. The amino acid substitutions and deletion affected the arising peptide pattern and thus modifications between IgE-binding epitopes and bioactive peptides of the variants were found. The allergenic potential of these different peptides will be investigated by microarray immunoassay using sera from milk-sensitized individuals, as it was already demonstrated for bovine αs1-casein variants. PMID:26922739

  13. Individual variation of human S1P₁ coding sequence leads to heterogeneity in receptor function and drug interactions.

    PubMed

    Obinata, Hideru; Gutkind, Sarah; Stitham, Jeremiah; Okuno, Toshiaki; Yokomizo, Takehiko; Hwa, John; Hla, Timothy

    2014-12-01

    Sphingosine 1-phosphate receptor 1 (S1P₁), an abundantly-expressed G protein-coupled receptor which regulates key vascular and immune responses, is a therapeutic target in autoimmune diseases. Fingolimod/Gilenya (FTY720), an oral medication for relapsing-remitting multiple sclerosis, targets S1P₁ receptors on immune and neural cells to suppress neuroinflammation. However, suppression of endothelial S1P₁ receptors is associated with cardiac and vascular adverse effects. Here we report the genetic variations of the S1P₁ coding region from exon sequencing of >12,000 individuals and their functional consequences. We conducted functional analyses of 14 nonsynonymous single nucleotide polymorphisms (SNPs) of the S1PR1 gene. One SNP mutant (Arg¹²⁰ to Pro) failed to transmit sphingosine 1-phosphate (S1P)-induced intracellular signals such as calcium increase and activation of p44/42 MAPK and Akt. Two other mutants (Ile⁴⁵ to Thr and Gly³⁰⁵ to Cys) showed normal intracellular signals but impaired S1P-induced endocytosis, which made the receptor resistant to FTY720-induced degradation. Another SNP mutant (Arg¹³ to Gly) demonstrated protection from coronary artery disease in a high cardiovascular risk population. Individuals with this mutation showed a significantly lower percentage of multi-vessel coronary obstruction in a risk factor-matched case-control study. This study suggests that individual genetic variations of S1P₁ can influence receptor function and, therefore, infer differential disease risks and interaction with S1P₁-targeted therapeutics. PMID:25293589

  14. Results from the Worldwide Coma Morphology Campaign for Comet ISON (C/2012 S1)

    NASA Astrophysics Data System (ADS)

    Samarasinha, Nalin H.

    2014-11-01

    Comet ISON (C/2012 S1) was predicted to be a bright comet in late 2013 because of its extremely small perihelion distance of 2.7 solar radii. In anticipation of the likely bonanza of scientific results, we coordinated a worldwide campaign (http://www.psi.edu/ison) to obtain both dust and gas images of the comet. During the campaign, we have received many hundreds of images primarily from amateur astronomers but also from a number of professionals.Comet ISON showed dust structure in its coma at large heliocentric distances before water became the primary sublimating gas. The Hubble Space Telescope (HST) observed a dust feature in the coma at a heliocentric distance of 4.15 AU in April 2013 (Li et al. 2013, ApJL, 779, article id. L3). The enhancement of continuum images taken by team members Nick Howes and Ernesto Guido at the 2-m Liverpool Telescope in May 2013 at different multiple epochs clearly showed the same dust feature (e.g., http://remanzacco.blogspot.com/2013/05/comet-c2012-s1-ison-update-may-20-2013.html). During the northern-hemisphere summer, the solar elongation of ISON became too small for ground-based observations. The comet was again observable starting in August 2013 as the solar elongation started to increase. These observations, at much smaller heliocentric distances than those described earlier, did not show the same dust feature. No unambiguous dust or gas features were seen until about two weeks prior to the perihelion and the comet’s demise (i.e., until mid November 2013). Based on the observations taken more than two weeks prior to the perihelion, we place upper limits on the radial extent of any possible dust feature. This and other results based on the coma morphology campaign will be discussed at the DPS 2014 meeting. The results from the analysis will be published in the future and will include the entire campaign.We thank many amateur and professional observers who contributed to this effort and all observers will be individually

  15. [A Case of Advanced Gastric Cancer with Long-Term Survival after Chemotherapy with Combined S-1 and CPT-11].

    PubMed

    Hiratsuka, Miyuki; Ishibashi, Yuji; Suematsu, Yuki; Suda, Hiroshi; Takahashi, Miyuki; Saito, Hiroyuki; Omori, Keita; Morita, Akihiko; Wakabayashi, Kazuhiko; Ito, Yutaka

    2015-11-01

    Here, we report a 54-year-old man diagnosed with type 3 advanced gastric cancer who underwent a total gastrectomy and splenectomy plus D2 lymphadenectomy. The pathologic diagnosis was Stage Ⅳ (T3N0H0P0CY1M1). Sixteen courses of combined S-1/CPT-11 chemotherapy were completed, at which time the CPT-11 was discontinued because of malaise, and S-1 alone was continued for a year. The patient is well and has been recurrence-free for 7 years. Thus, he is considered a long- term survivor who was treated with combination S-1/CPT-11 chemotherapy. PMID:26805264

  16. Scaling of dynamic thermoelectric harvesting devices in the 1-100 cm3 range

    NASA Astrophysics Data System (ADS)

    Kiziroglou, M. E.; Elefsiniotis, A.; Kokorakis, N.; Wright, S. W.; Toh, T. T.; Mitcheson, P. D.; Schmid, U.; Becker, Th.; Yeatman, E. M.

    2015-05-01

    Aircraft sensors are typically cable powered, imposing a significant weight overhead. The exploitation of temperature variations during flight by a phase change material (PCM) based heat storage thermoelectric energy harvester, as an alternative power source in aeronautical applications, has recently been flight tested. In this work, a scaled-down and a scaled-up prototype are presented. Output energy of 4.1 J per gram of PCM from a typical flight cycle is demonstrated for the scaled-down device, and 3.2 J per gram of PCM for the scaled-up device. The observed performance improvement with scaling down is attributed to the reduction in temperature inhomogeneity inside the PCM. As an application demonstrator for dynamic thermoelectric harvesting devices, the output of a thermoelectric module is used to directly power a microcontroller for the generation of a pulse width modulation signal.

  17. Final report on the regional supplementary comparison APMP.AUV.A-S1

    NASA Astrophysics Data System (ADS)

    Plangsangmas, Virat; Leeudomwong, Surat; Scott, Andrew; Zhong, Bo; Huang, Yuchung

    2014-01-01

    A regional supplementary comparison APMP.AUV.A-S1 has been carried out for the measurement of sound pressure level, frequency and total distortion of a multi-frequency sound calibrator. The role of the Pilot laboratory was undertaken by the National Institute of Metrology (Thailand) (NIMT). The multi-frequency sound calibrator was circulated through thirteen National Metrology Institutes (NMIs). Two NMIs were added to the original time schedule after starting the circulation. The measurements took place between September 2008 and July 2010. This report includes the measurement results from all the participants. Supplementary Comparison Reference Values (SCRVs) have been determined from the results. Deviations from the SCRVs are mostly within declared expanded uncertainties. It has been found that a term for the inherent instability in this type of device needs to be included in any uncertainty budget, and a recommended minimum value of this has been given. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCAUV, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  18. Capture of Cometary Dust Grains in Impacts at 6.1 km s-1

    NASA Astrophysics Data System (ADS)

    Burchell, M. J.; Foster, N.; Kearsley, A.; Wozniakiewicz, P.

    2009-12-01

    The NASA Stardust mission to comet 81P/Wild 2 collected grains of cometary dust freshly ejected from the comet during a fly-by at a speed of 6.1 km s-1. These were captured on aluminum foils and in blocks of silica aerogel. The dust underwent a severe shock during capture. The nature of the shock process depends on the properties of the dust and the collecting media. On the aluminium, the shock process and impact damage is typical of that between high-density (or hard materials) at high velocity, resulting in craters lined with impactor residues. The peak shock pressures are estimated at 60-80 GPa. Two main crater types are seen, simple bowl shaped and multiple pit craters: these reflect the degree of consolidation of the original dust grain. Capture in the low density aerogel was via a more gradual slowing of the dust grains accompanied by a variety of effects on the grains (complete break up of weak grains vs. ablation of well consolidated grains). The relation between the structure of the dust grains and the resulting impact features in both collector materials is discussed.

  19. Morphometric analysis of feedforward pathways from the primary somatosensory area (S1) of rats

    PubMed Central

    de Sá, A.L.; Bahia, C.P.; Correa, V.C.; Dias, I.A.; Batista, C.; Gomes-Leal, W.; Pinho, A.L.S.; Houzel, J.C.; Picanço-Diniz, C.W.; Pereira, A.

    2016-01-01

    We used biotinylated dextran amine (BDA) to anterogradely label individual axons projecting from primary somatosensory cortex (S1) to four different cortical areas in rats. A major goal was to determine whether axon terminals in these target areas shared morphometric similarities based on the shape of individual terminal arbors and the density of two bouton types: en passant (Bp) and terminaux (Bt). Evidence from tridimensional reconstructions of isolated axon terminal fragments (n=111) did support a degree of morphological heterogeneity establishing two broad groups of axon terminals. Morphological parameters associated with the complexity of terminal arbors and the proportion of beaded Bp vs stalked Bt were found to differ significantly in these two groups following a discriminant function statistical analysis across axon fragments. Interestingly, both groups occurred in all four target areas, possibly consistent with a commonality of presynaptic processing of tactile information. These findings lay the ground for additional work aiming to investigate synaptic function at the single bouton level and see how this might be associated with emerging properties in postsynaptic targets. PMID:27191604

  20. First observation of mesospheric wind shear as high as 330 m s-1 km-1

    NASA Astrophysics Data System (ADS)

    Wu, Yong-Fu; Widdel, H.-U.; Offermann, D.

    1995-09-01

    Mesospheric wind profiles with an altitude resolution of 25 m have been obtained by means of radar tracking of foil chaff clouds. Such experiments were performed during winter 1990 at Biscarrosse, France (44°N, 1°W). On one flight, a wind shear as high as 330 m s-1 km-1 at 87.4 km and a region of dynamical instability between 86 and 88 km was measured. This wind shear is believed to be the largest value ever measured in the mesosphere. The region of dynamical instability results from a superposition of two wave motions, and is found to link well with enhanced turbulence and small-scale wave activity. Acknowledgements. I thank D. R. McDiarmid of the Herzberg Institute of Astrophysics, National Research Council, Canada, for important ideas and discussions during the development of this work. I thank the referees for useful comments which have improved the paper. I also thank E.M. Poulter of NIWA for helpful suggestions, and for reading the manuscript and making useful comments. The work was supported by contract CO1309 of the New Zealand Foundation for Research, Science and Technology. Topical Editor C.-G. Fälthammar thanks K. Mursula and W. J. Hughes for their help in evaluating this paper.--> Correspondence to: W. Allan-->

  1. Observation of an exotic baryon with S=+1 in photoproduction from the proton.

    PubMed

    Kubarovsky, V; Guo, L; Weygand, D P; Stoler, P; Battaglieri, M; DeVita, R; Adams, G; Li, Ji; Nozar, M; Salgado, C; Ambrozewicz, P; Anciant, E; Anghinolfi, M; Asavapibhop, B; Audit, G; Auger, T; Avakian, H; Bagdasaryan, H; Ball, J P; Barrow, S; Beard, K; Bektasoglu, M; Bellis, M; Benmouna, N; Berman, B L; Bianchi, N; Biselli, A S; Boiarinov, S; Bouchigny, S; Bradford, R; Branford, D; Briscoe, W J; Brooks, W K; Burkert, V D; Butuceanu, C; Calarco, J R; Carman, D S; Carnahan, B; Cetina, C; Chen, S; Ciciani, L; Cole, P L; Connelly, J; Cords, D; Corvisiero, P; Crabb, D; Crannell, H; Cummings, J P; De Sanctis, E; Degtyarenko, P V; Denizli, H; Dennis, L; Dharmawardane, K V; Djalali, C; Dodge, G E; Doughty, D; Dragovitsch, P; Dugger, M; Dytman, S; Dzyubak, O P; Egiyan, H; Egiyan, K S; Elouadrhiri, L; Empl, A; Eugenio, P; Farhi, L; Fatemi, R; Feuerbach, R J; Ficenec, J; Forest, T A; Frolov, V; Funsten, H; Gaff, S J; Garçon, M; Gavalian, G; Gilfoyle, G P; Giovanetti, K L; Girard, P; Gothe, R; Gordon, C I O; Griffioen, K; Guidal, M; Guillo, M; Gyurjyan, V; Hadjidakis, C; Hakobyan, R S; Hancock, D; Hardie, J; Heddle, D; Heimberg, P; Hersman, F W; Hicks, K; Holtrop, M; Hu, J; Ilieva, Y; Ito, M M; Jenkins, D; Joo, K; Juengst, H G; Kelley, J H; Khandaker, M; Kim, K Y; Kim, K; Kim, W; Klein, F J; Klimenko, A V; Klusman, M; Kossov, M; Kramer, L H; Kuhn, S E; Kuhn, J; Lachniet, J; Laget, J M; Langheinrich, J; Lawrence, D; Longhi, A; Lukashin, K; Major, R W; Manak, J J; Marchand, C; McAleer, S; McNabb, J W C; Mecking, B A; Mehrabyan, S; Melone, J J; Mestayer, M D; Meyer, C A; Mikhailov, K; Minehart, R; Mirazita, M; Miskimen, R; Mokeev, V; Morand, L; Morrow, S A; Mozer, M U; Muccifora, V; Mueller, J; Mutchler, G S; Napolitano, J; Nasseripour, R; Nelson, S O; Niccolai, S; Niculescu, G; Niculescu, I; Niczyporuk, B B; Niyazov, R A; O'Brien, J T; O'Rielly, G V; Opper, A K; Osipenko, M; Park, K; Pasyuk, E; Peterson, G; Philips, S A; Pivnyuk, N; Pocanic, D; Pogorelko, O; Polli, E; Pozdniakov, S; Preedom, B M; Price, J W; Prok, Y; Protopopescu, D; Qin, L M; Raue, B A; Riccardi, G; Ripani, M; Ritchie, B G; Ronchetti, F; Rossi, P; Rowntree, D; Rubin, P D; Sabatié, F; Sabourov, K; Santoro, J P; Sapunenko, V; Sargsyan, M; Schumacher, R A; Serov, V S; Shafi, A; Sharabian, Y G; Shaw, J; Simionatto, S; Skabelin, A V; Smith, E S; Smith, T; Smith, L C; Sober, D I; Spraker, M; Stavinsky, A; Stepanyan, S; Strakovsky, I I; Strauch, S; Taiuti, M; Taylor, S; Tedeschi, D J; Thoma, U; Thompson, R; Todor, L; Tur, C; Ungaro, M; Vineyard, M F; Vlassov, A V; Wang, K; Weinstein, L B; Weisberg, A; Whisnant, C S; Wolin, E; Wood, M H; Yegneswaran, A; Yun, J

    2004-01-23

    The reaction gamma p-->pi(+)K(-)K(+)n was studied at Jefferson Laboratory using a tagged photon beam with an energy range of 3-5.47 GeV. A narrow baryon state with strangeness S=+1 and mass M=1555+/-10 MeV/c(2) was observed in the nK(+) invariant mass spectrum. The peak's width is consistent with the CLAS resolution (FWHM=26 MeV/c(2)), and its statistical significance is (7.8+/-1.0)sigma. A baryon with positive strangeness has exotic structure and cannot be described in the framework of the naive constituent quark model. The mass of the observed state is consistent with the mass predicted by the chiral soliton model for the Theta(+) baryon. In addition, the pK(+) invariant mass distribution was analyzed in the reaction gamma p-->K(-)K(+)p with high statistics in search of doubly charged exotic baryon states. No resonance structures were found in this spectrum. PMID:14753864

  2. Variable NK cell receptors exemplified by human KIR3DL1/S1.

    PubMed

    Parham, Peter; Norman, Paul J; Abi-Rached, Laurent; Guethlein, Lisbeth A

    2011-07-01

    Variegated expression of variable NK cell receptors for polymorphic MHC class I broadens the range of an individual's NK cell response and the capacity for populations and species to survive disease epidemics and population bottlenecks. On evolutionary time scales, this component of immunity is exceptionally dynamic, unstable, and short-lived, being dependent on coevolution of ligands and receptors subject to varying, competing selection pressures. Consequently these systems of variable NK cell receptors are largely species specific and have recruited different classes of glycoprotein, even within the primate order of mammals. Such disparity helps to explain substantial differences in NK cell biology between humans and animal models, for which the population genetics is largely ignored. KIR3DL1/S1, which recognizes the Bw4 epitope of HLA-A and -B and is the most extensively studied of the variable NK cell receptors, exemplifies how variation in all possible parameters of function is recruited to diversify the human NK cell response. PMID:21690332

  3. Far-ultraviolet Observations of Comet C/2012 S1 (ISON) from FORTIS

    NASA Astrophysics Data System (ADS)

    McCandliss, Stephan R.; Feldman, Paul D.; Weaver, Harold; Fleming, Brian; Redwine, Keith; Li, Mary J.; Kutyrev, Alexander; Moseley, S. Harvey

    2016-09-01

    We have used the unique far-UV imaging capability offered by a sounding-rocket-borne instrument to acquire observations of C/2012 S1 (ISON) when its angular separation with respect to the Sun was 26.°3 on 2013 November 20.49. At the time of observation, the comet’s heliocentric distance and velocity relative to the Sun were r h = 0.43 au and {\\dot{r}}h = ‑62.7 km s‑1. Images dominated by C i λ1657 and H i λ1216 were acquired over a 106 × 106 km2 region. The water production rate implied by the Lyα observations is constrained to be {Q}{{{H}}2{{O}}}≈ 8 × 1029 s‑1 while the neutral carbon production rate was {Q}C ≈ 4 ×1028 s‑1. The radial profile of C i was consistent with it being a dissociation product of a parent molecule with a lifetime τ ∼ 5 × 104 s, favoring a parent other than CO. We constrain the Q CO production rate to {5}-7.5+1.5 × 1028 s‑1 with 1σ errors derived from photon statistics. The upper limit on the Q CO/{Q}{{{H}}2{{O}}} is ≲6%.

  4. HUBBLE SPACE TELESCOPE OBSERVATIONS OF THE NUCLEUS OF COMET C/2012 S1 (ISON)

    SciTech Connect

    Lamy, Philippe L.; Toth, Imre; Weaver, Harold A.

    2014-10-10

    We report on the analysis of several sequences of broadband visible images of comet C/2012 S1 (ISON) taken with the Wide Field Camera 3 of the Hubble Space Telescope on 2013 April 10, May 8, October 9, and November 1 in an attempt to detect and characterize its nucleus. Whereas the overwhelming coma precluded the detection of the nucleus in the first two sequences, the contrast was sufficient in early October to unambiguously retrieve the signal from the nucleus. Two images taken within a few minutes led to similar V magnitudes for the nucleus of 21.97 and 22.0 with a 1σ uncertainty of 0.065. Assuming a standard value for the geometric albedo (0.04) and a linear phase function with a coefficient of 0.04 mag deg{sup –1}, these V values imply that the nucleus radius is 0.68 ± 0.02 km. Although this result does depend on these two assumptions, we argue that the radius most likely lies in the range 0.6-0.9 km. This result is consistent with the constraints derived from the water production rates reported by Combi et al. The last sequence of images in 2013 November revealed temporal variation of the innermost coma. If attributed to a single rotating jet, this coma brightness variation suggests the rotational period of the nucleus may be close to ∼10.4 hr.

  5. Extending the Family of V(4+) S=(1/2) Kagome Antiferromagnets.

    PubMed

    Clark, Lucy; Aidoudi, Farida H; Black, Cameron; Arachchige, Kasun S A; Slawin, Alexandra M Z; Morris, Russell E; Lightfoot, Philip

    2015-12-14

    The ionothermal synthesis, structure, and magnetic susceptibility of a novel inorganic-organic hybrid material, imidazolium vanadium(III,IV) oxyfluoride [C3 H5 N2 ][V9 O6 F24 (H2 O)2 ] (ImVOF) are presented. The structure consists of inorganic vanadium oxyfluoride slabs with kagome layers of V(4+) S=${{ 1/2 }}$ ions separated by a mixed valence layer. These inorganic slabs are intercalated with imidazolium cations. Quinuclidinium (Q) and pyrazinium (Pyz) cations can also be incorporated into the hybrid structure type to give QVOF and PyzVOF analogues, respectively. The highly frustrated topology of the inorganic slabs, along with the quantum nature of the magnetism associated with V(4+) , means that these materials are excellent candidates to host exotic magnetic ground states, such as the highly sought quantum spin liquid. Magnetic susceptibility measurements of all samples suggest an absence of conventional long-range magnetic order down to 2 K despite considerable antiferromagnetic exchange. PMID:26515792

  6. Unusual Magnetic Response of an S = 1 Antiferromagetic Linear-Chain Material

    NASA Astrophysics Data System (ADS)

    Xia, J. S.; Meisel, M. W.; Ozarowski, A.; Spurgeon, P. M.; Graham, A. G.; Manson, J. L.

    2015-03-01

    An S = 1 antiferromagnetic polymeric chain, [Ni(HF2)(3-Clpy)4]BF4 (py = pyridine), has been identified to have nearest-neighbor antiferromagnetic interaction J /kB = 4 . 86 K and single-ion anisotropy D /kB = 4 . 3 K, while avoiding long-range order down to 25 mK. With D / J = 0 . 88 , this system is close to the D / J ~ 1 gapless quantum critical point between the topologically distinct Haldane and Large- D phases. The magnetization was studied over a range of temperatures, 50 mK <= T <= 1 K, and magnetic fields, B <= 10 T. The results allow an upper bound of the critical field, Bc, which closes the Haldane gap, to be estimated. Specifically, Bc <= (35 +/- 10) mT, which is close to the predicted 46 mT, when using the reported2 values of J, D, and g. In low fields, the magnetic signal increases with decreasing T for 400 mK < T < 800 mK but is independent of T for 50 mK <= T <= 400 mK. This observation is consistent with a significant increase in the specific heat arising from the accumulation of entropy in the vicinity of the quantum critical point. Supported by NSF via DMR-1202033 (MWM), DMR-1306158 (JLM), and DMR-1157490 (NHMFL).

  7. Observation of an Exotic Baryon with S=+1 in Photoproduction from the Proton

    SciTech Connect

    Valery Kubarovsky; Lei Guo; Dennis Weygand; Paul Stoler; Marco Battaglieri; Raffaella De Vita; Gary Adams; Ji Li; Mina Nozar; Carlos Salgado; Pawel Ambrozewicz; Eric Anciant; Marco Anghinolfi; Burin Asavapibhop; Gerard Audit; Thierry Auger; Harutyun AVAKIAN; Hovhannes Baghdasaryan; Jacques Ball; Steve Barrow

    2004-01-01

    The reaction {gamma}p {yields} {pi}{sup +} K{sup -} K{sup +}n was studied at Jefferson Lab using a tagged photon beam with an energy range of 3-5.47 GeV. A narrow baryon state with strangeness S = +1 and mass M = 1555 {+-} 10 MeV/c{sup 2} was observed in the nK{sup +} invariant mass spectrum. The peak's width is consistent with the CLAS resolution (FWHM = 26 MeV/c{sup 2}), and its statistical significance is 7.8 {+-} 1.0 {sigma}. A baryon with positive strangeness has exotic structure and cannot be described in the framework of the naive constituent quark model. The mass of the observed state is consistent with the mass predicted by a chiral soliton model for the {Theta}{sup +} baryon. In addition, the pK{sup +} invariant mass distribution was analyzed in the reaction {gamma} p {yields} K{sup -} K{sup +}p with high statistics in search of doubly-charged exotic baryon states. No resonance structures were found in this spectrum.

  8. Magnetism in S = 1 / 2 Double Perovskites with Strong Spin-Orbit Interactions

    NASA Astrophysics Data System (ADS)

    Ishizuka, Hiroaki; Balents, Leon

    2015-03-01

    Motivated by recent studies on heavy-element double-perovskite (DP) compounds, we theoretically studied spin models on a FCC lattice with anisotropic interactions. In these systems, competition/cooperation of spin, orbital, and the lattice degrees of freedoms in the presence of the strong-spin orbit coupling is of particular interest. In a previous theoretical study, the magnetic phase diagrams of DP compounds with 5d1 electron configuration was studied using a model with four-fold degenerated single-ion state. On the other hand, a recent experiment on a DP material, Ba2Na2OsO6, reported that the compound is likely to be an effective S = 1 / 2 magnet. Inspired by the experimental observation, we considered spin models with symmetry-allowed anisotropic nearest-neighbor interactions. By a combination of various analytical and numerical techniques, we present the magnetic phase diagram of the model and the effect of thermal and quantum fluctuations. In particular, we show that fluctuations induce < 110 > anisotropy of magnetic moments. We also discuss a possible ``nematic'' phase driven by spin-phonon couplings.

  9. PS-1/S1 picosecond streak camera application for multichannel laser system diagnostics

    SciTech Connect

    Garanin, S G; Bel'kov, S A; Rogozhnikov, G S; Rukavishnikov, N N; Romanov, V V; Voronich, I N; Vorob'ev, N S; Gornostaev, P B; Lozovoi, V I; Shchelev, M Ya

    2014-08-31

    A PS-1/S1 picosecond image-tube streak camera (ITSC) with slit scan (streak camera), developed and manufactured at the General Physics Institute RAS, has been used to measure the spatiotemporal characteristics of ultrashort laser pulses generated by a petawatt-power laser installation 'FEMTO' at the Institute of Laser Physics Research in Sarov. It is found that such a camera is suitable for measuring the spatial and temporal parameters of single laser pulses with an accuracy of about one picosecond. It is shown that the intensity time profile of a train of picosecond pulses may be precisely defined for the pulses separated in time by a few picoseconds. The camera allows the contrast of radiation to be determined with a high (no less than 10{sup 3}) accuracy; spatial distribution of the laser pulses can be measured with an accuracy of tens of microns, and the temporal separation of single laser pulses can be identified with an accuracy of 1 – 1.5 ps. (extreme light fields and their applications)

  10. Hard X-ray XAFS beamline, BL5S1, at AichiSR

    NASA Astrophysics Data System (ADS)

    Tabuchi, M.; Asakura, H.; Morimoto, H.; Watanabe, N.; Takeda, Y.

    2016-05-01

    A XAFS beamline, BL5S1, had been operated at Aichi Synchrotron Radiation Center, Japan since March 2013. The beamline was designed for the measurements in the energy range from 5 to 20 keV. The photon flux of 6 x 1010 at around 9 keV and beam spot size of 0.5 x 0.3 mm at sample position are as good as designed. For the standard transmission XAFS measurement, both of the step- and quick- scan modes are available. Energy resolution at around 9keV is good enough to discuss the energy shift of the order of 0.1 eV or higher even when the measurements are conducted in the quick-scan mode. With several kinds of detectors for fluorescence and/or CEY detection mode measurements, and various kinds of sample holders which are supported by the XAFS measurement software, users easily obtain spectra for their samples. Such a standard, well operated and easy to access XAFS beamline must be very important to broaden the base of the XAFS society further.

  11. The weak measurement process and the weak value of spin for metastable helium 23S1

    NASA Astrophysics Data System (ADS)

    Monachello, Vincenzo; Barker, Peter; Flack, Robert; Hiley, Basil

    2016-05-01

    An experiment is being designed and constructed in order to measure the weak value of spin for an atomic system. The principle of the ``weak measurement'' process was first proposed by Aharonov, Albert and Vaidman, and describes a scenario in which a system is weakly coupled to a pointer between well-defined pre- and post-selected states. This experiment will utilise a pulsed supersonic beam of spin-1 metastable Helium (He*) atoms in the 23S1 state. The spin of the pre-selected He* atoms will be weakly coupled to its centre-of-mass. During its flight, the atomic beam will be prepared in a desired quantum state and travel through two inhomogeneous magnets (weak and strong) which both comprise the ``weak measurement'' process. The deviation of the post-selected ms = + 1 state as measured using a micro-channel plate, phosphor screen and CCD camera setup will allow for the determination of the weak value of spin. This poster will report on the methods used and the experimental realisation.

  12. M-theory on S1/Z2: new facts from a careful analysis1

    NASA Astrophysics Data System (ADS)

    Bilal, Adel; Derendinger, Jean-Pierre; Sauser, Roger

    2000-06-01

    We carefully reexamine the issues of solving the modified Bianchi identity, anomaly cancellations and flux quantization in the S 1/ Z2 orbifold of M-theory using the boundary-free "upstairs" formalism, avoiding several misconceptions present in earlier literature. While the solution for the four-form G to the modified Bianchi identity appears to depend on an arbitrary parameter b, we show that requiring G to be globally well-defined, i.e., invariant under small and large gauge and local Lorentz transformations, fixes b=1. This value also is necessary for a consistent reduction to the heterotic string in the small-radius limit. Insisting on properly defining all fields on the circle, we find that there is a previously unnoticed additional contribution to the anomaly inflow from the eleven-dimensional topological term. Anomaly cancellation then requires a quadratic relation between b and the combination λ 6/κ 4 of the gauge and gravitational coupling constants λ and κ. This contrasts with previous beliefs that anomaly cancellation would give a cubic equation for b. We observe that our solution for G automatically satisfies integer or half-integer flux quantization for the appropriate cycles. We explicitly write out the anomaly cancelling terms of the heterotic string as inherited from the M-theory approach. They differ from the usual ones by the addition of a well-defined local counterterm. We also show how five-branes enter our analysis.

  13. Far-ultraviolet Observations of Comet C/2012 S1 (ISON) from FORTIS

    NASA Astrophysics Data System (ADS)

    McCandliss, Stephan R.; Feldman, Paul D.; Weaver, Harold; Fleming, Brian; Redwine, Keith; Li, Mary J.; Kutyrev, Alexander; Moseley, S. Harvey

    2016-09-01

    We have used the unique far-UV imaging capability offered by a sounding-rocket-borne instrument to acquire observations of C/2012 S1 (ISON) when its angular separation with respect to the Sun was 26.°3 on 2013 November 20.49. At the time of observation, the comet’s heliocentric distance and velocity relative to the Sun were r h = 0.43 au and {\\dot{r}}h = ‑62.7 km s‑1. Images dominated by C i λ1657 and H i λ1216 were acquired over a 106 × 106 km2 region. The water production rate implied by the Lyα observations is constrained to be {Q}{{{H}}2{{O}}}≈ 8 × 1029 s‑1 while the neutral carbon production rate was {Q}C ≈ 4 ×1028 s‑1. The radial profile of C i was consistent with it being a dissociation product of a parent molecule with a lifetime τ ˜ 5 × 104 s, favoring a parent other than CO. We constrain the Q CO production rate to {5}-7.5+1.5 × 1028 s‑1 with 1σ errors derived from photon statistics. The upper limit on the Q CO/{Q}{{{H}}2{{O}}} is ≲6%.

  14. Global magnetic fluctuations in S-1 Spheromak plasmas and relaxation toward a minimum-energy state

    SciTech Connect

    Janos, A.; Hart, G.W.; Nam, C.H.; Yamada, M.

    1985-05-01

    Globally coherent modes have been observed during formation in the S-1 Spheromak plasma by analysis of magnetic field fluctuations measured from outside the plasma. The modes are of low n number (2 less than or equal to n less than or equal to 5), where n is defined by the functional dependence e/sup in phi/ of the fluctuation on toroidal angle phi. These modes are shown to be related to flux conversion and plasma relaxation toward a minimum-energy state during the spheromak formation. The modes are active while the q profile is rapidly changing, with q on-axis, q/sub 0/, rising to 0.7. A significant finding is the temporal progression through the n = 5, 4, 3, 2; m = 1 mode sequence as q rises through rational fractions m/n. During formation, peak amplitudes of the n = 2, 3, 4 modes relative to the unperturbed field have been observed as high as 20%, while more typical amplitudes are below 5%.

  15. Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy.

    PubMed

    Rolando, Monica; Escoll, Pedro; Nora, Tamara; Botti, Joëlle; Boitez, Valérie; Bedia, Carmen; Daniels, Craig; Abraham, Gilu; Stogios, Peter J; Skarina, Tatiana; Christophe, Charlotte; Dervins-Ravault, Delphine; Cazalet, Christel; Hilbi, Hubert; Rupasinghe, Thusitha W T; Tull, Dedreia; McConville, Malcolm J; Ong, Sze Ying; Hartland, Elizabeth L; Codogno, Patrice; Levade, Thierry; Naderer, Thomas; Savchenko, Alexei; Buchrieser, Carmen

    2016-02-16

    Autophagy is an essential component of innate immunity, enabling the detection and elimination of intracellular pathogens. Legionella pneumophila, an intracellular pathogen that can cause a severe pneumonia in humans, is able to modulate autophagy through the action of effector proteins that are translocated into the host cell by the pathogen's Dot/Icm type IV secretion system. Many of these effectors share structural and sequence similarity with eukaryotic proteins. Indeed, phylogenetic analyses have indicated their acquisition by horizontal gene transfer from a eukaryotic host. Here we report that L. pneumophila translocates the effector protein sphingosine-1 phosphate lyase (LpSpl) to target the host sphingosine biosynthesis and to curtail autophagy. Our structural characterization of LpSpl and its comparison with human SPL reveals high structural conservation, thus supporting prior phylogenetic analysis. We show that LpSpl possesses S1P lyase activity that was abrogated by mutation of the catalytic site residues. L. pneumophila triggers the reduction of several sphingolipids critical for macrophage function in an LpSpl-dependent and -independent manner. LpSpl activity alone was sufficient to prevent an increase in sphingosine levels in infected host cells and to inhibit autophagy during macrophage infection. LpSpl was required for efficient infection of A/J mice, highlighting an important virulence role for this effector. Thus, we have uncovered a previously unidentified mechanism used by intracellular pathogens to inhibit autophagy, namely the disruption of host sphingolipid biosynthesis. PMID:26831115

  16. PS-1/S1 picosecond streak camera application for multichannel laser system diagnostics

    NASA Astrophysics Data System (ADS)

    Garanin, S. G.; Bel'kov, S. A.; Rogozhnikov, G. S.; Rukavishnikov, N. N.; Romanov, V. V.; Voronich, I. N.; Vorob'ev, N. S.; Gornostaev, P. B.; Lozovoi, V. I.; Shchelev, M. Ya

    2014-08-01

    A PS-1/S1 picosecond image-tube streak camera (ITSC) with slit scan (streak camera), developed and manufactured at the General Physics Institute RAS, has been used to measure the spatiotemporal characteristics of ultrashort laser pulses generated by a petawatt-power laser installation 'FEMTO' at the Institute of Laser Physics Research in Sarov. It is found that such a camera is suitable for measuring the spatial and temporal parameters of single laser pulses with an accuracy of about one picosecond. It is shown that the intensity time profile of a train of picosecond pulses may be precisely defined for the pulses separated in time by a few picoseconds. The camera allows the contrast of radiation to be determined with a high (no less than 103) accuracy; spatial distribution of the laser pulses can be measured with an accuracy of tens of microns, and the temporal separation of single laser pulses can be identified with an accuracy of 1 - 1.5 ps.

  17. Magnetic excitations from an S = 1/2 antiferromagnetic tetramer system Cu2 PO 4OH

    NASA Astrophysics Data System (ADS)

    Matsuda, M.; Abernathy, D. L.; Totsuka, K.; Belik, A. A.

    2011-03-01

    Cu 2 PO4 OH is a candidate material for the S = 1/2 diamond-shaped antiferromagnetic tetramer system. The magnetic susceptibility shows a spin-gap behavior and the exchange interaction J was estimated to be 138 K. Since there have not been so many experimental studies in the spin tetramer systems, it is important to clarify the magnetism in this compound. We have performed inelastic neutron scattering experiments on a powder sample of Cu 2 PO4 OH on a chopper neutron spectrometer ARCS installed at SNS at ORNL in order to study the magnetic excitations from the tetramer spin system. We have clearly observed two magnetic excitations at ~ 12 and ~ 20 meV, whose widths in energy are broader than the instrumental resolution. It was found that the energy levels cannot be explained with the simple antiferromagnetic tetramer model with only nearest-neighbor interaction. We will discuss the results including further-neighbor interactions. A. A. Belik et al., Inorg. Chem. 46, 8684 (2007).

  18. Magnetic order and magnon coherent state in double exchange s=1/2 lattices

    SciTech Connect

    Lopez-Aguilar, F.

    2010-02-15

    Starting from trial wave functions and by minimizing the total energy, we obtain the ground state (GS) of a magnetic system in which there is competition between two exchange interactions: one of them between localized and unlocalized spins and another one among the spins of a Heisenberg s=1/2 lattice. This analysis allows us to analyze directly a particular case of a magnetic ground state: a magnon gas whose collective wave function presents similarities with the coherent state of the electromagnetic field which is the basis for the laser. The Kondo coupling becomes concomitant with the external magnetic field which can control the number of magnons. The corresponding Zeeman effect provoked by the magnetic external field plus the Kondo interaction energy compete with the spin-spin Heisenberg exchange of the localized magnetic lattices. The fruit of the competition of these three interactions is the existence of a collective state which can be represented with an oscillation with one only frequency which has a minimum uncertainty and therefore it is a most similar quantum state to a classical wave. This collective state for determined crystal conditions, values of Kondo coupling strength, external B values and Heisenberg J{sub ij}-parameters tends to be a minimal energy state, and then, this coherent state, can transit to a magnon Bose-Einstein condensate (BEC). The passing from the minimal coherent state towards the BEC condensation is thermodynamically analyzed and we have deduced the critical temperature of this phase transition.

  19. Legionella pneumophila S1P-lyase targets host sphingolipid metabolism and restrains autophagy

    PubMed Central

    Rolando, Monica; Escoll, Pedro; Nora, Tamara; Botti, Joëlle; Boitez, Valérie; Daniels, Craig; Abraham, Gilu; Stogios, Peter J.; Skarina, Tatiana; Christophe, Charlotte; Dervins-Ravault, Delphine; Cazalet, Christel; Hilbi, Hubert; Rupasinghe, Thusitha W. T.; Tull, Dedreia; McConville, Malcolm J.; Ong, Sze Ying; Hartland, Elizabeth L.; Codogno, Patrice; Levade, Thierry; Naderer, Thomas; Savchenko, Alexei; Buchrieser, Carmen

    2016-01-01

    Autophagy is an essential component of innate immunity, enabling the detection and elimination of intracellular pathogens. Legionella pneumophila, an intracellular pathogen that can cause a severe pneumonia in humans, is able to modulate autophagy through the action of effector proteins that are translocated into the host cell by the pathogen’s Dot/Icm type IV secretion system. Many of these effectors share structural and sequence similarity with eukaryotic proteins. Indeed, phylogenetic analyses have indicated their acquisition by horizontal gene transfer from a eukaryotic host. Here we report that L. pneumophila translocates the effector protein sphingosine-1 phosphate lyase (LpSpl) to target the host sphingosine biosynthesis and to curtail autophagy. Our structural characterization of LpSpl and its comparison with human SPL reveals high structural conservation, thus supporting prior phylogenetic analysis. We show that LpSpl possesses S1P lyase activity that was abrogated by mutation of the catalytic site residues. L. pneumophila triggers the reduction of several sphingolipids critical for macrophage function in an LpSpl-dependent and -independent manner. LpSpl activity alone was sufficient to prevent an increase in sphingosine levels in infected host cells and to inhibit autophagy during macrophage infection. LpSpl was required for efficient infection of A/J mice, highlighting an important virulence role for this effector. Thus, we have uncovered a previously unidentified mechanism used by intracellular pathogens to inhibit autophagy, namely the disruption of host sphingolipid biosynthesis. PMID:26831115

  20. Diel vertical migration of zooplankton at the S1 biogeochemical mooring revealed from acoustic backscattering strength

    NASA Astrophysics Data System (ADS)

    Inoue, Ryuichiro; Kitamura, Minoru; Fujiki, Tetsuichi

    2016-02-01

    We examined the diel vertical migration of zooplankton by using the backscatter strength obtained from moored acoustic Doppler current profilers at mooring site S1 in the North Pacific subtropical gyre. There was seasonal variability in the vertical distribution and migration of the high-backscatter layers in that they became deeper than the euphotic zone (<100 m) in winter and were confined above this depth in other seasons. Seasonal changes in daylight hours also affected the timing of the diel migration. We found that lunar cycles affected vertical distributions of zooplankton near the surface by changing the light intensity. Physical events, such as mixed-layer deepening and restratification and the passage of a mesoscale eddy, also affected zooplankton behavior possibly by changing food environment in the euphotic zone. Since the comparison with net samples indicated that the backscatter likely represents the bulk biomass, the accuracy of biomass estimates based on net samples could be influenced by the high temporal variability of zooplankton distributions.

  1. Fermionic Representation of a Spin S chain Using subalgebra of SU(2S+1)

    NASA Astrophysics Data System (ADS)

    Duki, Solomon F.; Yu, Yi-Kuo

    2014-03-01

    Quantum mechanical spins behave neither as pure bosonic nor as pure fermionic operators. Over the years many different kinds of important mappings have been introduced that transform spins systems in to either multi-bosonic or multi-fermionic systems. These mappings have often successfully transformed some of the most difficult many body problems into simpler ones. Moreover, because symmetries that are hidden in one representation can be manifested in other representations, such mappings are also helpful in uncovering hidden symmetries in physical problems. Examples of such transformations include the Holstein-Primakoff, the Schwinger bosons, the Matsubara-Matsuda, and the Jordan-Wigner transformations. Despite their success for low dimensional systems and at smaller values of spins, these transformations become ineffective in reducing the degree of difficulty of correlated systems when the system dimension increase or when the underlying system has a higher spin values. In the context of a spin chain, we introduce a new spin fermion transformation for arbitrary spin S using the subalgebra of the bigger su(2S+1) algebra and discuss its potential applications in physical problems. This research was supported by the Intramural Research Program of the NIH, National Library of Medicine.

  2. Multiflavor QCD∗ on R3 ×S1: Studying transition from Abelian to non-Abelian confinement

    NASA Astrophysics Data System (ADS)

    Shifman, M.; Ünsal, M.

    2009-11-01

    The center-stabilized multiflavor QCD∗ theories formulated on R3 ×S1 exhibit both Abelian and non-Abelian confinement as a function of the S1 radius, similar to the Seiberg-Witten theory as a function of the mass deformation parameter. For sufficiently small number of flavors and small r (S1), we show occurrence of a mass gap in gauge fluctuations, and linear confinement. This is a regime of confinement without continuous chiral symmetry breaking (χSB). Unlike one-flavor theories where there is no phase transition in r (S1), the multiflavor theories possess a single phase transition associated with breaking of the continuous χS. We conjecture that the scale of the χSB is parametrically tied up with the scale of Abelian to non-Abelian confinement transition.

  3. A new method for the calculation of Sommerfeld screening parameter s1 in x-ray spectra

    NASA Astrophysics Data System (ADS)

    Misra, U. D.; Chaturvedi, S.

    2001-06-01

    The paper describes a new method for the calculation of the Sommerfeld screening parameter s1. It requires neither the knowledge of the energy separations of spin doublet levels nor is it based on the application of the Hertz law. The only data required for the calculation are the experimental energy values of the level concerned for the series of elements belonging to the same subshell in which the element in the question is situated. As an illustration the values of s1 are calculated for the L1, L 2 and L3 levels for elements belonging to the 4f subshell and these are found to be in excellent agreement with those published earlier by Gokhale and Misra. The method brings out the constancy of s1(L1 L3) - s1(L1) in a natural way and may thus be regarded as providing theoretical explanation of the Hertz law.

  4. Transsacral transdiscal L5-S1 screws for the management of high-grade spondylolisthesis in an adolescent.

    PubMed

    Palejwala, Ali; Fridley, Jared; Jea, Andrew

    2016-06-01

    The surgical management of high-grade spondylolisthesis in adolescents remains a controversial issue. Because the basic procedure, posterolateral fusion, is associated with a significant rate of pseudarthrosis and listhesis progression, there is a pressing need for alternative surgical techniques. In the present report, the authors describe the case of an adolescent patient with significant low-back pain who was found to have Grade IV spondylolisthesis at L5-S1 that was treated with transsacral transdiscal screw fixation. Bilateral pedicle screws were placed starting from the top of the S-1 pedicle, across the L5-S1 intervertebral disc space, and into the L-5 body. At 14 months after surgery, the patient had considerable improvement in his pain and radiographic fusion across L5-S1. The authors conclude that transsacral transdiscal pedicle screws may serve as an efficacious and safe option for the correction of high-grade spondylolisthesis in adolescent patients. PMID:26894520

  5. [A Case of Alternate-Day Treatment with S-1 in a Patient with Multiple Lung Metastases of Colon Cancer].

    PubMed

    Kamata, Arimichi; Kano, Tsunehisa; Hagiwara, Hideyuki; Sarukawa, Hideki; Wada, Yudai; Miyamae, Taku; Koizumi, Masaki; Takahashi, Kazuhiro; Abe, Yutaka; Natori, Joji; Uchiyama, Kiichiro

    2016-03-01

    The recommended regimen for S-1 internal use is 4 weeks of daily medication and 2 weeks of drug holiday. However, we experience many cases where changing the regimen is ineffective because of adverse events. This time, we report a favorable case of alternate-day treatment with S-1 in an elderly patient with multiple lung metastases of colon cancer. An 84-year-old woman, performance status 2, was diagnosed as having colon cancer and multiple lung metastases. After operation of the colon, she received chemotherapy with the S-1 alternate-day treatment. The lung metastases decreased remarkably, and she was able to continue the treatment without significant adverse events. She has been receiving the treatment without progression for more than 18 months now. The alternate-day treatment with S-1 is reported as a cure with anticancer efficacy and few adverse events. This treatment seems to be a useful chemotherapy for elderly patients with colon cancer. PMID:27067859

  6. Effects of S1 Cleavage on the Structure, Surface Export, and Signaling Activity of Human Notch1 and Notch2

    PubMed Central

    Gordon, Wendy R.; Vardar-Ulu, Didem; L'Heureux, Sarah; Ashworth, Todd; Malecki, Michael J.; Sanchez-Irizarry, Cheryll; McArthur, Debbie G.; Histen, Gavin; Mitchell, Jennifer L.; Aster, Jon C.; Blacklow, Stephen C.

    2009-01-01

    Background Notch receptors are normally cleaved during maturation by a furin-like protease at an extracellular site termed S1, creating a heterodimer of non-covalently associated subunits. The S1 site lies within a key negative regulatory region (NRR) of the receptor, which contains three highly conserved Lin12/Notch repeats and a heterodimerization domain (HD) that interact to prevent premature signaling in the absence of ligands. Because the role of S1 cleavage in Notch signaling remains unresolved, we investigated the effect of S1 cleavage on the structure, surface trafficking and ligand-mediated activation of human Notch1 and Notch2, as well as on ligand-independent activation of Notch1 by mutations found in human leukemia. Principal Findings The X-ray structure of the Notch1 NRR after furin cleavage shows little change when compared with that of an engineered Notch1 NRR lacking the S1-cleavage loop. Likewise, NMR studies of the Notch2 HD domain show that the loop containing the S1 site can be removed or cleaved without causing a substantial change in its structure. However, Notch1 and Notch2 receptors engineered to resist S1 cleavage exhibit unexpected differences in surface delivery and signaling competence: S1-resistant Notch1 receptors exhibit decreased, but detectable, surface expression and ligand-mediated receptor activation, whereas S1-resistant Notch2 receptors are fully competent for cell surface delivery and for activation by ligands. Variable dependence on S1 cleavage also extends to T-ALL-associated NRR mutations, as common class 1 mutations display variable decrements in ligand-independent activation when introduced into furin-resistant receptors, whereas a class 2 mutation exhibits increased signaling activity. Conclusions/Significance S1 cleavage has distinct effects on the surface expression of Notch1 and Notch2, but is not generally required for physiologic or pathophysiologic activation of Notch proteins. These findings are consistent with

  7. Effects of S1 Cleavage on the Structure, Surface Export, and Signaling Activity of Human Notch1 and Notch2

    SciTech Connect

    Gordon, Wendy R.; Vardar-Ulu, Didem; L'Heureux, Sarah; Ashworth, Todd; Malecki, Michael J.; Sanchez-Irizarry, Cheryll; McArthur, Debbie G.; Histen, Gavin; Mitchell, Jennifer L.; Aster, Jon C.; Blacklow, Stephen C.

    2009-09-25

    Notch receptors are normally cleaved during maturation by a furin-like protease at an extracellular site termed S1, creating a heterodimer of non-covalently associated subunits. The S1 site lies within a key negative regulatory region (NRR) of the receptor, which contains three highly conserved Lin12/Notch repeats and a heterodimerization domain (HD) that interact to prevent premature signaling in the absence of ligands. Because the role of S1 cleavage in Notch signaling remains unresolved, we investigated the effect of S1 cleavage on the structure, surface trafficking and ligand-mediated activation of human Notch1 and Notch2, as well as on ligand-independent activation of Notch1 by mutations found in human leukemia. The X-ray structure of the Notch1 NRR after furin cleavage shows little change when compared with that of an engineered Notch1 NRR lacking the S1-cleavage loop. Likewise, NMR studies of the Notch2 HD domain show that the loop containing the S1 site can be removed or cleaved without causing a substantial change in its structure. However, Notch1 and Notch2 receptors engineered to resist S1 cleavage exhibit unexpected differences in surface delivery and signaling competence: S1-resistant Notch1 receptors exhibit decreased, but detectable, surface expression and ligand-mediated receptor activation, whereas S1-resistant Notch2 receptors are fully competent for cell surface delivery and for activation by ligands. Variable dependence on S1 cleavage also extends to T-ALL-associated NRR mutations, as common class 1 mutations display variable decrements in ligand-independent activation when introduced into furin-resistant receptors, whereas a class 2 mutation exhibits increased signaling activity. S1 cleavage has distinct effects on the surface expression of Notch1 and Notch2, but is not generally required for physiologic or pathophysiologic activation of Notch proteins. These findings are consistent with models for receptor activation in which ligand-binding or

  8. The elusive S2 state, the S1/S2 splitting, and the excimer states of the benzene dimer.

    PubMed

    Balmer, Franziska A; Trachsel, Maria A; van der Avoird, Ad; Leutwyler, Samuel

    2015-06-21

    We observe the weak S0 → S2 transitions of the T-shaped benzene dimers (Bz)2 and (Bz-d6)2 about 250 cm(-1) and 220 cm(-1) above their respective S0 → S1 electronic origins using two-color resonant two-photon ionization spectroscopy. Spin-component scaled (SCS) second-order approximate coupled-cluster (CC2) calculations predict that for the tipped T-shaped geometry, the S0 → S2 electronic oscillator strength fel(S2) is ∼10 times smaller than fel(S1) and the S2 state lies ∼240 cm(-1) above S1, in excellent agreement with experiment. The S0 → S1 (ππ(∗)) transition is mainly localized on the "stem" benzene, with a minor stem → cap charge-transfer contribution; the S0 → S2 transition is mainly localized on the "cap" benzene. The orbitals, electronic oscillator strengths fel(S1) and fel(S2), and transition frequencies depend strongly on the tipping angle ω between the two Bz moieties. The SCS-CC2 calculated S1 and S2 excitation energies at different T-shaped, stacked-parallel and parallel-displaced stationary points of the (Bz)2 ground-state surface allow to construct approximate S1 and S2 potential energy surfaces and reveal their relation to the "excimer" states at the stacked-parallel geometry. The fel(S1) and fel(S2) transition dipole moments at the C2v-symmetric T-shape, parallel-displaced and stacked-parallel geometries are either zero or ∼10 times smaller than at the tipped T-shaped geometry. This unusual property of the S0 → S1 and S0 → S2 transition-dipole moment surfaces of (Bz)2 restricts its observation by electronic spectroscopy to the tipped and tilted T-shaped geometries; the other ground-state geometries are impossible or extremely difficult to observe. The S0 → S1/S2 spectra of (Bz)2 are compared to those of imidazole ⋅ (Bz)2, which has a rigid triangular structure with a tilted (Bz)2 subunit. The S0 → S1/ S2 transitions of imidazole-(benzene)2 lie at similar energies as those of (Bz)2, confirming our assignment of the

  9. Potential of MuS1 Transgenic Tobacco for Phytoremediation of the Urban Soils Contaminated with Cadmium

    NASA Astrophysics Data System (ADS)

    Kim, K. H.; Kim, Y. N.; Kim, S. H.

    2010-05-01

    Urban soils are prone to contamination by trace elements such as Cd, Cu, Pb and Zn. Phytoremediation is one of the attractive remediation methods for soils contaminated with trace elements due to its non-destructive and environmentally-friendly characteristic. Scientists have tried to find hyper-accumulator plants in nature or to develop transgenic plant through genetic engineering. This study was carried out to identify a potential of MuS1 transgenic tobacco for phytoremediation of the urban soils contaminated with Cd. MuS1 is known as a multiple stress related gene with several lines. The previous study using RT-PCR showed that the expression of MuS1 gene in tobacco plant induced tolerance to Cd stress. For this study, MuS1 transgenic tobacco and wild-type tobacco (control) were cultivated in a hydroponic system treated with Cd (0, 50, 100 and 200μM Cd) for 3 weeks. At harvest, both tobacco and nutrient solution were collected and were analyzed for Cd. Effect of Cd treatment on morphological change of the tobacco leaves was also observed by variable-pressure scanning electron microscopy (VP-SEM). The tolerance of MuS1 transgenic tobacco to Cd stress was better than that of wild-type tobacco at all Cd levels. Especially, wild-type tobacco showed chlorosis and withering with 200μM Cd treatment, whereas MuS1 transgenic tobacco gradually recovered from Cd damage. Wild-type tobacco accumulated more Cd (4.65mg per plant) than MuS1 transgenic tobacco (2.37mg per plant) with 200μM Cd treatment. Cd translocation rate from root to leaves was 81.8 % for wild-type tobacco compared to 37.1 % for MuS1 transgenic tobacco. Result of VP-SEM showed that the number of trichome in the leaves for wild-type tobacco increased in comparison with that for untreated samples after 3 weeks, while that for MuS1 transgenic tobacco was not changed by Cd treatment. Results showed that the mechanism of the recovery of the MuS1 tobacco plant was not by high level of Cd uptake and accumulation

  10. Effect of hemopoietic microenvironment on splenic suppressor macrophages in congenitally anemic mice of genotype S1/sup d/

    SciTech Connect

    Not Available

    1985-01-01

    Mechanisms underlying mononuclear phagocyte specialization are being probed by studying suppressor macrophages as a reference population in mouse models with impaired blood monocyte formation. Splenic suppressor macrophages, defined by PGE-mediated inhibition of Con A-induced T lymphocyte proliferation are induced by the i.p. administration of Corynebacterium parvum (CP). Mice severely depleted of bone marrow and blood monocytes by treatment with /sup 89/Sr fail to show this suppressor macrophages response to CP, although macrophages-forming stem cells, assessed as splenic M-CFC in vitro, are increased 20-fold. These observations suggest that radiosensitive bone marrow stem cells are necessary for the generation of both suppressor macrophages and monocytes and that one such stem cell may be common to both types of mononuclear phagocytes. This notion was explored further by employing congenitally anemic mice of the genotype S1/S1 superscript d in which the hemopoietic microenvironment is genetically defective and thus unable to support the proliferation, differentiation, and function of stem cells. The congenital defect was found to be additionally expressed in the S1/S1/sup d/ mouse by a monocytopenia of less than 10% of the values in normal congenic littermate controls and by the failure of splenic M-CFC to increase in response to cp. PGE-producing suppressor macrophages expressing Fcy2b receptors, however, were induced by CP in S1/S1/sup d/ mice with no significant diminution of suppressor activity.

  11. Antigenic modules in the N-terminal S1 region of the transmissible gastroenteritis virus spike protein

    PubMed Central

    Reguera, Juan; Ordoño, Desiderio; Santiago, César; Enjuanes, Luis

    2011-01-01

    The N-terminal S1 region of the transmissible gastroenteritis virus (TGEV) spike (S) glycoprotein contains four antigenic sites (C, B, D and A, from the N- to the C-terminal end) and is engaged in host-cell receptor recognition. The most N-terminal portion of the S1 region, which comprises antigenic sites C and B, is needed for the enteric tropism of TGEV, whereas the major antigenic site A at the C-terminal moiety is required for both respiratory and enteric cell tropism, and is engaged in recognition of the aminopeptidase N (APN) receptor. This study determined the kinetics for binding of a soluble S1 protein to the APN protein. Moreover, the S1 region of the TGEV S protein was dissected, with the aim of identifying discrete modules displaying unique antigenic sites and receptor-binding functions. Following protease treatments and mammalian cell expression methods, four modules or domains (D1–D4) were defined at the S1 region. Papain treatment identified an N-terminal domain (D1) resistant to proteolysis, whereas receptor binding defined a soluble and functional APN receptor-binding domain (D3). This domain was recognized by neutralizing antibodies belonging to the antigenic site A and therefore could be used as an immunogen for the prevention of viral infection. The organization of the four modules in the S1 region of the TGEV S glycoprotein is discussed. PMID:21228126

  12. Interaction between the Linker, Pre-S1, and TRP Domains Determines Folding, Assembly, and Trafficking of TRPV Channels.

    PubMed

    Garcia-Elias, Anna; Berna-Erro, Alejandro; Rubio-Moscardo, Fanny; Pardo-Pastor, Carlos; Mrkonjić, Sanela; Sepúlveda, Romina V; Vicente, Rubén; González-Nilo, Fernando; Valverde, Miguel A

    2015-08-01

    Functional transient receptor potential (TRP) channels result from the assembly of four subunits. Here, we show an interaction between the pre-S1, TRP, and the ankyrin repeat domain (ARD)-S1 linker domains of TRPV1 and TRPV4 that is essential for proper channel assembly. Neutralization of TRPV4 pre-S1 K462 resulted in protein retention in the ER, defective glycosylation and trafficking, and unresponsiveness to TRPV4-activating stimuli. Similar results were obtained with the equivalent mutation in TRPV1 pre-S1. Molecular dynamics simulations revealed that TRPV4-K462 generated an alternating hydrogen network with E745 (TRP box) and D425 (pre-S1 linker), and that K462Q mutation affected subunit folding. Consistently, single TRPV4-E745A or TRPV4-D425A mutations moderately affected TRPV4 biogenesis while double TRPV4-D425A/E745A mutation resumed the TRPV4-K462Q phenotype. Thus, the interaction between pre-S1, TRP, and linker domains is mandatory to generate a structural conformation that allows the contacts between adjacent subunits to promote correct assembly and trafficking to the plasma membrane. PMID:26146187

  13. A systematic methodology for large scale compound screening: A case study on the discovery of novel S1PL inhibitors.

    PubMed

    Deniz, Utku; Ozkirimli, Elif; Ulgen, Kutlu O

    2016-01-01

    Decrease in sphingosine 1-phosphate (S1P) concentration induces migration of pathogenic T cells to the blood stream, disrupts the CNS and it is implicated in multiple sclerosis (MS), a progressive inflammatory disorder of the central nervous system (CNS), and Alzheimer's disease (AD). A promising treatment alternative for MS and AD is inhibition of the activity of the microsomal enzyme sphingosine 1-phosphate lyase (S1PL), which degrades intracellular S1P. This report describes an integrated systematic approach comprising virtual screening, molecular docking, substructure search and molecular dynamics simulation to discover novel S1PL inhibitors. Virtual screening of the ZINC database via ligand-based and structure-based pharmacophore models yielded 10000 hits. After molecular docking, common substructures of the top ranking hits were identified. The ligand binding poses were optimized by induced fit docking. MD simulations were performed on the complex structures to determine the stability of the S1PL-ligand complex and to calculate the binding free energy. Selectivity of the selected molecules was examined by docking them to hERG and cytochrome P450 receptors. As a final outcome, 15 compounds from different chemotypes were proposed as potential S1PL inhibitors. These molecules may guide future medicinal chemistry efforts in the discovery of new compounds against the destructive action of pathogenic T cells. PMID:26724452

  14. Role of JAK-STAT pathway in reducing cardiomyocytes hypoxia/reoxygenation injury induced by S1P postconditioning.

    PubMed

    Wang, Yuqing; Wang, Dongfei; Zhang, Lizhi; Ye, Fangyu; Li, Mengmeng; Wen, Ke

    2016-08-01

    This experiment was designed to explore the protection of sphingosine1-phosphate (S1P) postconditioning on rat myocardial cells injured by hypoxia/reoxygenation acting via the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signal pathway. The data showed that S1P could significantly increase cell viability, lower the rate of apoptosis, decrease the content of lactate dehydrogenase (LDH) and caspase3 activity in the culture medium, increase the activity of total superoxide dismutase (T-SOD) and manganese superoxide dismutase (Mn-SOD), reduce the loss of mitochondrial membrane potential and the fluorescence intensity of intracellular calcium, as well as increase the phosphorylation of JAK2 and STAT3 in comparison with the H/R group. When the JAK inhibitor AG490 or the STAT inhibitor stattic were added, the effects of S1P were inhibited. Our date shows that S1P protects H9c2 cells from hypoxia/reoxygenation injury and that the protection by S1P was inhibited by AG490 and stattic. Therefore S1P protects H9c2 cells against hypoxia/reoxygenation injury via the JAK-STAT pathway. PMID:27215146

  15. Novel alkaline earth copper germanates with ferro and antiferromagnetic S=1/2 chains

    SciTech Connect

    Brandao, Paula; Reis, Mario S; Gai, Zheng; Moreira Dos Santos, Antonio F

    2013-01-01

    Two new alkaline earth copper(II) germanates were hydrothermally synthesized: CaCuGeO4 center dot H2O (1) and BaCu2Ge3O9 center dot H2O (2), and their structures determined by single crystal X-ray diffraction. Compound (1) crystallizes in space group P2(1)/c with a=5.1320(2) angstrom, b=16.1637(5) angstrom, c=5.4818(2) angstrom, beta=102.609(2)degrees, V=443.76(3) angstrom(3) and Z=4. This copper germanate contains layers of composition [CuGeO4](infinity)(2-) comprising CuO4 square planes and GeO4 tetrahedra with calcium and water molecules in the inter-layer space. Compound (2) crystallizes in the Cmcm space group with a=5.5593(3) angstrom, b=10.8606(9) angstrom, c=13.5409(8) angstrom, V=817.56(9) angstrom(3) and Z=4. This structure contains GeO6 and CuO6 octahedra as well as GeO4 tetrahedra, forming a three-dimensional network of interconnecting six-membered ring channels. The magnetic susceptibility for both samples can be interpreted as S=1/2 chains, in agreement with the copper topology observed in the crystal structure. The susceptibility of (1) exhibits a Bonner-Fisher type behavior, resulting from antiferromagnetic intra-chain interactions without three-dimensional ordering down to 5 K-the lowest measured temperature. This observation, together with the absence of super-exchange paths between the copper chains, make this system particularly promising for the study of low dimensional magnetism. The magnetic properties of (2) show a very weak ferromagnetic near-neighbor interaction along the chain. In this compound a peak the chi T plot seems to indicate the onset of interchain antiferromagentic correlations. However, no ordering temperature is detected in the susceptibility data.

  16. OUTGASSING BEHAVIOR OF C/2012 S1 (ISON) FROM 2011 SEPTEMBER TO 2013 JUNE

    SciTech Connect

    Meech, Karen J.; Yang, Bin; Kleyna, Jan; Chiang, Hsin-Fang; Riesen, Timm; Keane, Jacqueline V.; Reipurth, Bo; Hsieh, Henry H.; Ansdell, Megan; Hainaut, Olivier; Vincent, Jean-Baptiste; Boehnhardt, Hermann; Fitzsimmons, Alan; Rector, Travis; Michaud, Peter; Milani, Giannantonio; Bryssinck, Erik; Ligustri, Rolando; Trabatti, Roberto; Tozzi, Gian-Paolo; and others

    2013-10-20

    We report photometric observations for comet C/2012 S1 (ISON) obtained during the time period immediately after discovery (r = 6.28 AU) until it moved into solar conjunction in mid-2013 June using the UH2.2 m, and Gemini North 8 m telescopes on Mauna Kea, the Lowell 1.8 m in Flagstaff, the Calar Alto 1.2 m telescope in Spain, the VYSOS-5 telescopes on Mauna Loa Hawaii and data from the CARA network. Additional pre-discovery data from the Pan STARRS1 survey extends the light curve back to 2011 September 30 (r = 9.4 AU). The images showed a similar tail morphology due to small micron sized particles throughout 2013. Observations at submillimeter wavelengths using the James Clerk Maxwell Telescope on 15 nights between 2013 March 9 (r = 4.52 AU) and June 16 (r = 3.35 AU) were used to search for CO and HCN rotation lines. No gas was detected, with upper limits for CO ranging between 3.5-4.5 × 10{sup 27} molecules s{sup –1}. Combined with published water production rate estimates we have generated ice sublimation models consistent with the photometric light curve. The inbound light curve is likely controlled by sublimation of CO{sub 2}. At these distances water is not a strong contributor to the outgassing. We also infer that there was a long slow outburst of activity beginning in late 2011 peaking in mid-2013 January (r ∼ 5 AU) at which point the activity decreased again through 2013 June. We suggest that this outburst was driven by CO injecting large water ice grains into the coma. Observations as the comet came out of solar conjunction seem to confirm our models.

  17. UNUSUAL WATER PRODUCTION ACTIVITY OF COMET C/2012 S1 (ISON): OUTBURSTS AND CONTINUOUS FRAGMENTATION

    SciTech Connect

    Combi, M. R.; Fougere, N.; Mäkinen, J. T. T.; Bertaux, J.-L.; Quémerais, E.

    2014-06-10

    The Solar Wind ANisotropies (SWAN) all-sky hydrogen Lyα camera on the SOlar and Heliospheric Observer (SOHO) satellite observed the hydrogen coma of comet C/2012 S1 (ISON) for most of the last month of its activity from 2013 October 24 to November 24, ending just 4 days before perihelion and its final disruption. The water production rate of the comet was determined from these observations. SOHO has been operating in a halo orbit around the Earth-Sun L1 Lagrange point since its launch in late 1995. Most water vapor produced by comets is ultimately photodissociated into two H atoms and one O atom producing a huge hydrogen coma that is routinely observed in the daily SWAN images in comets of sufficient brightness. Water production rates were calculated from 22 images over most of the last month of the pre-perihelion apparition. The water production rate increased very slowly on average from October 24.9 until November 12.9, staying between 1.8 and 3.4 × 10{sup 28} s{sup –1}, after which it increased dramatically, reaching 1.6 to 2 × 10{sup 30} s{sup –1} from November 21.6 to 23.6. It was not detected after perihelion on December 3.7 when it should have been visible. We examine the active surface area necessary to explain the water production rate and its variation and are able to place constraints on the physical size of the original nucleus necessary to account for the large amount of activity from November 12.9 and until just before perihelion.

  18. Comet C/2012 S1 (ISON) coma composition at ~4 au from HST observations

    NASA Astrophysics Data System (ADS)

    Zubko, Evgenij; Videen, Gorden; Hines, Dean C.; Shkuratov, Yuriy; Kaydash, Vadym; Muinonen, Karri; Knight, Matthew M.; Sitko, Michael L.; Lisse, Carey M.; Mutchler, Max; Wooden, Diane H.; Li, Jian-Yang; Kobayashi, Hiroshi

    2015-12-01

    We analyze the first color and polarization images of Comet ISON (C/2012 S1) taken during two measurement campaigns of the Hubble Space Telescope (HST) on UTC 2013 April 10 and May 8, when the phase angles of Comet ISON were α≈13.7° and 12.2°, respectively. We model the particles in the coma using highly irregular agglomerated debris particles. Even though the observations were made over a small range of phase angle, the data still place significant constraints on the material properties of the cometary coma. The different photo-polarimetric responses are indicative of spatial chemical heterogeneity of coma in Comet ISON. For instance, at small projected distances to the nucleus (<500 km), our modeling suggests the cometary particles are composed predominantly of small, highly absorbing particles, such as amorphous carbon and/or organics material heavily irradiated with UV radiation; whereas, at longer projected distances (>1000 km), the refractive index of the particles is consistent with organic matter slightly processed with UV radiation, tholins, Mg-Fe silicates, and/or Mg-rich silicates contaminated with ~10% (by volume) amorphous carbon. The modeling suggests low relative abundances of particles with low material absorption in the visible, i.e., Im(m)≤0.02. Such particles were detected unambiguously in other comets in the vicinity of nucleus through very strong negative polarization near backscattering (P≈-6%) and very low positive polarization (P≈3-5%) at side scattering. These materials were previously attributed to Mg-rich silicates forming a refractory surface layer on the surface of cometary nuclei (Zubko et al., 2012). The absence of such particles in Comet ISON could imply an absence of such a layer on its nucleus.

  19. Nondestructive post-irradiation examination of Loop-1, S1 and B1 rods

    SciTech Connect

    Bratton, R.L.

    1997-05-01

    As a part of the Pacific Northwest National Laboratory`s Tritium Target Development Program, eleven tritium target rods were irradiated in the Advanced Test Reactor located at the Idaho National Engineering and Environmental Laboratory during 1991. Both nondestructive and destructive post-irradiation examination on all eleven rods was planned under the Tritium Target Development Program. Funding for the program was reduced in 1991 resulting in the early removal of the program experiments before reaching their irradiation goals. Post-irradiation examination was only performed on one of the irradiated rods at the Pacific Northwest National Laboratory before the program was terminated in 1992. On December 6, 1995, the Secretary of Energy announced the pursuit of the Commercial Light-Water Reactor option for producing tritium establishing the Tritium Target Qualification Program at the Pacific Northwest National Laboratory. This program decided to pursue nondestructive and destructive post-irradiation examination of the ten remaining rods from the previous program. The ten rods comprise three experiments. The Loop-1 experiment irradiated eight target rods in a loop configuration for 217 irradiation days. The other two rods were irradiated in two separate irradiation experiments, designated as S1 and B1 for 143 effective full-power days, but at different power levels. After the ten rods were transferred from the ATR Canal to the Hot Fuels Examination Facility, the following examinations were performed: (1) visual examination and photography; (2) neutron radiography; (3) axial gamma scanning; (4) contact profilometry measurement; (5) bow and length measurements; (6) rod puncture and plenum gas analysis/measurement of plenum gas quantity; (7) void volume determination; and (8) internal pressure determination. This report presents the data collected during these examinations.

  20. Position , photometric and morphological monitoring of comet-sungrazer S/2012 S1 (ISON) in Kyiv

    NASA Astrophysics Data System (ADS)

    Churyumov, Klim; Baransky, Alexandr

    Comet-sungrazer C/2012 S1 (ISON) was observed at the observational station of Kyiv Shevchenko National University ( MPC 585 ) from 28 Sept. 2012 to 1 Nov. 2013 During the 16 nights of observation obtained and sent to the database MPC - 214 astromerical exact positions of the comet. In parallel with the astrometrical monitoring of the comet were obtained a series of photometrical observations of cometary central condensation (m_2) through filter R. During Oct. - Dec. 2012 a magnitude of the central condensation of the comet (m(2) ) increased gradually from 17.6(m) to 16.8(m) . In the period from Dec. 28, 2012 to Jan. 2, 2013 there was observed a jump of increasing of comet brightness by ampliitude 1.1(m) from 16.8(m) to 15.7(m) , which was initiated by a sharp increasing of numbers of the sunspot : on Dec. 31, 2012 the Wolf number was 87 , and on Jan. 4 it reached of a values 167. Until the end of Feb. 2013 a cometary magnitude reached a values 15.4(m) . During Feb.- May 2013 the magnitude of the comet almost did not change. In the summer of 2013 , the comet did not observe because the small elongation of the comet. In autumn 2013 , a month before perihelion passage , the comet was observed during temporal interval Oct. 20 - Nov. 1. In the course of this period cometary magnitude of the central condensation rapidly increased from 13.4(m) to 11.6(m) . In the anti-solar direction the large tail was observed. Near the head in the direction of the comet tail a bright - helically twisted jet was observed.

  1. European S1 guideline for the treatment of hidradenitis suppurativa/acne inversa.

    PubMed

    Zouboulis, C C; Desai, N; Emtestam, L; Hunger, R E; Ioannides, D; Juhász, I; Lapins, J; Matusiak, L; Prens, E P; Revuz, J; Schneider-Burrus, S; Szepietowski, J C; van der Zee, H H; Jemec, G B E

    2015-04-01

    Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle that usually presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body, most commonly the axillae, inguinal and anogenital regions. A mean disease incidence of 6.0 per 100,000 person-years and an average prevalence of 1% has been reported in Europe. HS has the highest impact on patients' quality of life among all assessed dermatological diseases. HS is associated with a variety of concomitant and secondary diseases, such as obesity, metabolic syndrome, inflammatory bowel disease, e.g. Crohn's disease, spondyloarthropathy, follicular occlusion syndrome and other hyperergic diseases. The central pathogenic event in HS is believed to be the occlusion of the upper part of the hair follicle leading to a perifollicular lympho-histiocytic inflammation. A highly significant association between the prevalence of HS and current smoking (Odds ratio 12.55) and overweight (Odds ratio 1.1 for each body mass index unit) has been documented. The European S1 HS guideline suggests that the disease should be treated based on its individual subjective impact and objective severity. Locally recurring lesions can be treated by classical surgery or LASER techniques, whereas medical treatment either as monotherapy or in combination with radical surgery is more appropriate for widely spread lesions. Medical therapy may include antibiotics (clindamycin plus rifampicine, tetracyclines), acitretin and biologics (adalimumab, infliximab). A Hurley severity grade-relevant treatment of HS is recommended by the expert group following a treatment algorithm. Adjuvant measurements, such as pain management, treatment of superinfections, weight loss and tobacco abstinence have to be considered. PMID:25640693

  2. Sphingosine-1-phosphate induces COX-2 expression and PGE2 production in human granulosa cells through a S1P1/3-mediated YAP signaling.

    PubMed

    Cheng, Jung-Chien; Chang, Hsun-Ming; Liu, Pang-Pin; Leung, Peter C K

    2016-06-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that can regulate various physiological and pathological processes. The expression of S1P has been detected in human follicular fluid. In addition, two S1P receptors, S1P1 and S1P3, are expressed at a high level in human granulosa cells. Cyclooxygenase-2 (COX-2)-derived prostaglandin E2 (PGE2) production plays a critical role in the regulation of ovulation. However, thus far, the effect of S1P on COX-2 expression and PGE2 production in human granulosa cells remains unknown. In the present study, our results demonstrated that treatment with S1P significantly induced COX-2, but not COX-1, expression and increased PGE2 production in human granulosa cells. The stimulatory effects of S1P on COX-2 expression and PGE2 production were attenuated by treatment with specific antagonist of S1P1 or S1P3 and siRNA-mediated knockdown of S1P1 or S1P3. In addition, the COX-2 expression was induced by S1P1 or S1P3 agonist treatment. Interestingly, treatment with S1P activated YAP signaling via S1P1 and S1P3. Moreover, knockdown of YAP partially attenuated S1P-induced COX-2 expression and PGE2 production. These results provide evidence that S1P induces COX-2 expression and PGE2 production in human granulosa cells through a S1P1/3-mediated YAP signaling pathway. PMID:26994820

  3. Feasibility of oral administration of S-1 as adjuvant chemotherapy in gastric cancer: 4-week S-1 administration followed by 2-week rest vs. 2-week administration followed by 1-week rest

    PubMed Central

    YAMATSUJI, TOMOKI; FUJIWARA, YASUHIRO; MATSUMOTO, HIDEO; HATO, SHINJI; NAMIKAWA, TSUTOMU; HANAZAKI, KAZUHIRO; TAKAOKA, MUNENORI; HAYASHI, JIRO; SHIGEMITSU, KAORI; YOSHIDA, KAZUHIRO; URAKAMI, ATSUSHI; UNO, FUTOSHI; NISHIZAKI, MASAHIKO; KAGAWA, SHUNSUKE; NINOMIYA, MOTOKI; FUJIWARA, TOSHIYOSHI; HIRAI, TOSHIHIRO; NAKAMURA, MASAFUMI; HAISA, MINORU; NAOMOTO, YOSHIO

    2015-01-01

    In 2006, the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) demonstrated that S-1 is an effective adjuvant therapy for gastric cancer. Following that study, S-1 has been used as the standard adjuvant therapy for gastric cancer in Japan. However, the 1-year completion rate was only 65.8% in the ACTS-GC study and feasibility remains a critical issue. We conducted a study to evaluate the feasibility of 2 weekly administration regimens of S-1 as adjuvant chemotherapy in gastric cancer. The criteria for eligibility included histologically proven stage II (excluding T1), IIIA or IIIB gastric cancer with D2 lymph-node dissection. The patients were randomly assigned to either arm A (S-1 administration for 4 weeks followed by 2 weeks of rest) or arm B (S-1 administration for 2 weeks followed by 1 week of rest). In each arm, treatment was continued for 12 months unless recurrence or severe adverse events were observed. The primary endpoint was feasibility (protocol treatment completion rate). The secondary endpoints were safety, relapse-free survival and overall survival. A total of 47 patients were assigned to arms A or B between May, 2008 and February, 2010. During the first interim analysis, the protocol treatment completion rates in arms A and B were 83 and 100%, respectively at 6 months and 49 and 89%, respectively, at 12 months (P=0.0046). Therefore, S-1 administration for 2 weeks followed by 1 week rest was more feasible as adjuvant chemotherapy in gastric cancer. Grade 3 adverse events in arm A included fatigue (8.0%), anorexia (8.0%), nausea (4.0%), vomiting (4.0%) and hand-foot syndrome (4.0%), whereas none were observed in arm B. There were no reported grade 4 adverse events in either arm. In conclusion, the 2-week S-1 administration followed by 1-week rest regimen appears to be a more feasible oral administration regimen for S-1 as adjuvant chemotherapy in gastric cancer. PMID:26137261

  4. 43 CFR 10.14 - Lineal descent and cultural affiliation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Hawaiian organization or by the common law system of descendence to a known Native American individual... Indian tribe or Native Hawaiian organization and an identifiable earlier group. All of the following... Hawaiian organization and the human remains, funerary objects, sacred objects, or objects of...

  5. 43 CFR 10.14 - Lineal descent and cultural affiliation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Hawaiian organization or by the common law system of descendence to a known Native American individual... Indian tribe or Native Hawaiian organization and an identifiable earlier group. All of the following... Hawaiian organization and the human remains, funerary objects, sacred objects, or objects of...

  6. 43 CFR 10.14 - Lineal descent and cultural affiliation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Hawaiian organization or by the common law system of descendence to a known Native American individual... Indian tribe or Native Hawaiian organization and an identifiable earlier group. All of the following... Hawaiian organization and the human remains, funerary objects, sacred objects, or objects of...

  7. 44 CFR 10.14 - Flood plains and wetlands.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Executive Order 11988, Flood Plain Management, and Executive Order 11990, Protection of Wetlands (44 CFR... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Flood plains and wetlands. 10... Flood plains and wetlands. For any action taken by FEMA in a flood plain or wetland, the provisions...

  8. 44 CFR 10.14 - Flood plains and wetlands.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Executive Order 11988, Flood Plain Management, and Executive Order 11990, Protection of Wetlands (44 CFR... 44 Emergency Management and Assistance 1 2013-10-01 2013-10-01 false Flood plains and wetlands. 10... Flood plains and wetlands. For any action taken by FEMA in a flood plain or wetland, the provisions...

  9. 44 CFR 10.14 - Flood plains and wetlands.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Executive Order 11988, Flood Plain Management, and Executive Order 11990, Protection of Wetlands (44 CFR... 44 Emergency Management and Assistance 1 2012-10-01 2011-10-01 true Flood plains and wetlands. 10... Flood plains and wetlands. For any action taken by FEMA in a flood plain or wetland, the provisions...

  10. 44 CFR 10.14 - Flood plains and wetlands.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Executive Order 11988, Flood Plain Management, and Executive Order 11990, Protection of Wetlands (44 CFR... 44 Emergency Management and Assistance 1 2011-10-01 2011-10-01 false Flood plains and wetlands. 10... Flood plains and wetlands. For any action taken by FEMA in a flood plain or wetland, the provisions...

  11. 44 CFR 10.14 - Flood plains and wetlands.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Executive Order 11988, Flood Plain Management, and Executive Order 11990, Protection of Wetlands (44 CFR... 44 Emergency Management and Assistance 1 2014-10-01 2014-10-01 false Flood plains and wetlands. 10... Flood plains and wetlands. For any action taken by FEMA in a flood plain or wetland, the provisions...

  12. Reduction of Aromatic and Heterocyclic Aromatic N-Hydroxylamines by Human Cytochrome P450 2S1

    PubMed Central

    Wang, Kai; Guengerich, F. Peter

    2013-01-01

    Many aromatic amines and heterocyclic aromatic amines (HAAs) are known carcinogens for animals and there is also strong evidence for some in human cancer. The activation of these compounds, including some arylamine drugs, involves N-hydroxylation, usually by cytochrome P450 enzymes (P450) in Family 1 (1A2, 1A1, and 1B1). We previously demonstrated that the bioactivation product of the anti-cancer agent 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203), an N-hydroxylamine, can be reduced by P450 2S1 to its amine precursor under anaerobic conditions and, to a lesser extent, under aerobic conditions (Wang, K., and Guengerich, F. P. (2012) Chem. Res. Toxicol. 25, 1740–1751). In the present study, we tested the hypothesis that P450 2S1 is involved in the reductive biotransformation of known carcinogenic aromatic amines and HAAs. The N-hydroxylamines of 4-aminobiphenyl (4-ABP), 2-naphthylamine (2-NA), and 2-aminofluorene (2-AF) were synthesized and found to be reduced by P450 2S1 under both anaerobic and aerobic conditions. The formation of amines due to P450 2S1 reduction also occurred under aerobic conditions but was less apparent because the competitive disproportionation reactions (of the N-hydroxylamines) also yielded amines. Further, some nitroso and nitro derivatives of the arylamines could also be reduced by P450 2S1. None of the amines tested were oxidized by P450 2S1. These results suggest that P450 2S1 may be involved in the reductive detoxication of several of the activated products of carcinogenic aromatic amines and HAAs. PMID:23682735

  13. S1P prophylaxis mitigates acute hypobaric hypoxia-induced molecular, biochemical, and metabolic disturbances: A preclinical report.

    PubMed

    Chawla, Sonam; Rahar, Babita; Saxena, Shweta

    2016-05-01

    Sphingosine-1-phosphate (S1P) is emerging to have hypoxic preconditioning potential in various preclinical studies. The study aims to evaluate the preclinical preconditioning efficacy of exogenously administered S1P against acute hypobaric hypoxia (HH)-induced pathological disturbances. Male Sprague Dawley rats (200 ± 20 g) were preconditioned with 1, 10, and 100 μg/kg body weight (b.w.) S1P (i.v.) for three consecutive days. On the third day, S1P preconditioned animals, along with hypoxia control animals, were exposed to HH equivalent to 7,620 m (280 mm Hg) for 6 h. Postexposure status of cardiac energy production, circulatory vasoactive mediators, pulmonary and cerebral oxidative damage, and inflammation were assessed. HH exposure led to cardiac energy deficit indicated by low ATP levels and pronounced AMPK activation levels, raised circulatory levels of brain natriuretic peptide and endothelin-1 with respect to total nitrate (NOx), redox imbalance, inflammation, and alterations in NOx levels in the pulmonary and cerebral tissues. These pathological precursors have been routinely reported to be coincident with high-altitude diseases. Preconditioning with S1P, especially 1 µg/kg b.w. dose, was seen to reverse the manifestation of these pathological disturbances. The protective efficacy could be attributed, at least in part, to enhanced activity of cardioprotective protein kinase C and activation of small GTPase Rac1, which led to further induction of hypoxia-adaptive molecular mediators: hypoxia-inducible factor (HIF)-1α and Hsp70. This is a first such report, to the best of our knowledge, elucidating the mechanism of exogenous S1P-mediated HIF-1α/Hsp70 induction. Conclusively, systemic preconditioning with 1 μg/kg b.w. S1P in rats protects against acute HH-induced pathological disturbances. © 2016 IUBMB Life 68(5):365-375, 2016. PMID:26959531

  14. Inhibition of preS1-hepatocyte interaction by an array of recombinant human antibodies from naturally recovered individuals

    PubMed Central

    Sankhyan, Anurag; Sharma, Chandresh; Dutta, Durgashree; Sharma, Tarang; Chosdol, Kunzang; Wakita, Takaji; Watashi, Koichi; Awasthi, Amit; Acharya, Subrat K.; Khanna, Navin; Tiwari, Ashutosh; Sinha, Subrata

    2016-01-01

    Neutralizing monoclonal antibodies are being found to be increasingly useful in viral infections. In hepatitis B infection, antibodies are proven to be useful for passive prophylaxis. The preS1 region (21–47a.a.) of HBV contains the viral hepatocyte-binding domain crucial for its attachment and infection of hepatocytes. Antibodies against this region are neutralizing and are best suited for immune-based neutralization of HBV, especially in view of their not recognizing decoy particles. Anti-preS1 (21–47a.a.) antibodies are present in serum of spontaneously recovered individuals. We generated a phage-displayed scFv library using circulating lymphocytes from these individuals and selected four preS1-peptide specific scFvs with markedly distinct sequences from this library. All the antibodies recognized the blood-derived and recombinant preS1 containing antigens. Each scFv showed a discrete binding signature, interacting with different amino acids within the preS1-peptide region. Ability to prevent binding of the preS1 protein (N-terminus 60a.a.) to HepG2 cells stably expressing hNTCP (HepG2-hNTCP-C4 cells), the HBV receptor on human hepatocytes was taken as a surrogate marker for neutralizing capacity. These antibodies inhibited preS1-hepatocyte interaction individually and even better in combination. Such a combination of potentially neutralizing recombinant antibodies with defined specificities could be used for preventing/managing HBV infections, including those by possible escape mutants. PMID:26888694

  15. Reduction of aromatic and heterocyclic aromatic N-hydroxylamines by human cytochrome P450 2S1.

    PubMed

    Wang, Kai; Guengerich, F Peter

    2013-06-17

    Many aromatic amines and heterocyclic aromatic amines (HAAs) are known carcinogens for animals, and there is also strong evidence of some in human cancer. The activation of these compounds, including some arylamine drugs, involves N-hydroxylation, usually by cytochrome P450 enzymes (P450) in Family 1 (1A2, 1A1, and 1B1). We previously demonstrated that the bioactivation product of the anticancer agent 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203), an N-hydroxylamine, can be reduced by P450 2S1 to its amine precursor under anaerobic conditions and, to a lesser extent, under aerobic conditions [Wang, K., and Guengerich, F. P. (2012) Chem. Res. Toxicol. 25, 1740-1751]. In the study presented here, we tested the hypothesis that P450 2S1 is involved in the reductive biotransformation of known carcinogenic aromatic amines and HAAs. The N-hydroxylamines of 4-aminobiphenyl (4-ABP), 2-naphthylamine (2-NA), and 2-aminofluorene (2-AF) were synthesized and found to be reduced by P450 2S1 under both anaerobic and aerobic conditions. The formation of amines due to P450 2S1 reduction also occurred under aerobic conditions but was less apparent because the competitive disproportionation reactions (of the N-hydroxylamines) also yielded amines. Further, some nitroso and nitro derivatives of the arylamines could also be reduced by P450 2S1. None of the amines tested were oxidized by P450 2S1. These results suggest that P450 2S1 may be involved in the reductive detoxication of several of the activated products of carcinogenic aromatic amines and HAAs. PMID:23682735

  16. Development History and Concept of an Oral Anticancer Agent S-1 (TS-1®): Its Clinical Usefulness and Future Vistas

    PubMed Central

    Shirasaka, Tetsuhiko

    2009-01-01

    Dushinsky et al. left a great gift to human beings with the discovery of 5-fluorouracil (5-FU). Approximately 50 years have elapsed from that discovery to the development of S-1 (TS-1®). The concept of developing an anticancer agent that simultaneously possesses both efficacy-enhancing and adverse reaction-reducing effects could be achieved only with a three-component combination drug. S-1 is an oral anticancer agent containing two biochemical modulators for 5-FU and tegafur (FT), a metabolically activated prodrug of 5-FU. The first modulator, 5-chloro-2,4-dihydroxypyridine (CDHP), enhances the pharmacological actions of 5-FU by potently inhibiting its degradation. The second modulator, potassium oxonate (Oxo), localizing in mucosal cells of the gastrointestinal (GI) tract after oral administration, reduces the incidence of GI toxicities by suppressing the activation of 5-FU in the GI tract. Thus, S-1 combines FT, CDHP and Oxo at a molar ratio of 1:0.4:1. In 1999–2007, S-1 was approved for the treatment of the following seven cancers: gastric, head and neck, colorectal, non-small cell lung, breast, pancreatic and biliary tract cancers. ‘S-1 and low-dose cisplatin therapy’ without provoking Grade 3 non-hematologic toxicities was proposed to enhance its clinical usefulness. Furthermore, ‘alternate-day S-1 regimen’ may improve the dosing schedule for 5-FU by utilizing its strongly time-dependent mode of action; the former is characterized by the low incidences of myelotoxicity and non-hematologic toxicities (e.g. ≤Grade 1 anorexia, fatigue, stomatitis, nausea, vomiting and taste alteration). These two approaches are considered to allow long-lasting therapy with S-1. PMID:19052037

  17. S1PR4 Signaling Attenuates ILT 7 Internalization To Limit IFN-α Production by Human Plasmacytoid Dendritic Cells.

    PubMed

    Dillmann, Christina; Ringel, Christian; Ringleb, Julia; Mora, Javier; Olesch, Catherine; Fink, Annika F; Roberts, Edward; Brüne, Bernhard; Weigert, Andreas

    2016-02-15

    Plasmacytoid dendritic cells (pDCs) produce large amounts of type I IFN in response to TLR7/9 ligands. This conveys antiviral effects, activates other immune cells (NK cells, conventional DCs, B, and T cells), and causes the induction and expansion of a strong inflammatory response. pDCs are key players in various type I IFN-driven autoimmune diseases such as systemic lupus erythematosus or psoriasis, but pDCs are also involved in (anti-)tumor immunity. The sphingolipid sphingosine-1-phosphate (S1P) signals through five G-protein-coupled receptors (S1PR1-5) to regulate, among other activities, immune cell migration and activation. The present study shows that S1P stimulation of human, primary pDCs substantially decreases IFN-α production after TLR7/9 activation with different types of CpG oligodeoxynucleotides or tick-borne encephalitis vaccine, which occurred in an S1PR4-dependent manner. Mechanistically, S1PR4 activation preserves the surface expression of the human pDC-specific inhibitory receptor Ig-like transcript 7. We provide novel information that Ig-like transcript 7 is rapidly internalized upon receptor-mediated endocytosis of TLR7/9 ligands to allow high IFN-α production. This is antagonized by S1PR4 signaling, thus decreasing TLR-induced IFN-α secretion. At a functional level, attenuated IFN-α production failed to alter Ag-driven T cell proliferation in pDC-dependent T cell activation assays, but shifted cytokine production of T cells from a Th1 (IFN-γ) to a regulatory (IL-10) profile. In conclusion, S1PR4 agonists block human pDC activation and may therefore be a promising tool to restrict pathogenic IFN-α production. PMID:26783340

  18. Salmonella Typhi OmpS1 and OmpS2 porins are potent protective immunogens with adjuvant properties

    PubMed Central

    Moreno-Eutimio, Mario A; Tenorio-Calvo, Alejandra; Pastelin-Palacios, Rodolfo; Perez-Shibayama, Christian; Gil-Cruz, Cristina; López-Santiago, Rubén; Baeza, Isabel; Fernández-Mora, Marcos; Bonifaz, Laura; Isibasi, Armando; Calva, Edmundo; López-Macías, Constantino

    2013-01-01

    Salmonella enterica serovar Typhi (S. Typhi) is the causal agent of typhoid fever, a disease that primarily affects developing countries. Various antigens from this bacterium have been reported to be targets of the immune response. Recently, the S. Typhi genome has been shown to encode two porins – OmpS1 and OmpS2 – which are expressed at low levels under in vitro culture conditions. In this study, we demonstrate that immunizing mice with either OmpS1 or OmpS2 induced production of specific, long-term antibody titres and conferred protection against S. Typhi challenge; in particular, OmpS1 was more immunogenic and conferred greater protective effects than OmpS2. We also found that OmpS1 is a Toll-like receptor 4 (TLR4) agonist, whereas OmpS2 is a TLR2 and TLR4 agonist. Both porins induced the production of tumour necrosis factor and interleukin-6, and OmpS2 was also able to induce interleukin-10 production. Furthermore, OmpS1 induced the over-expression of MHC II molecules in dendritic cells and OmpS2 induced the over-expression of CD40 molecules in macrophages and dendritic cells. Co-immunization of OmpS1 or OmpS2 with ovalbumin (OVA) increased anti-OVA antibody titres, the duration and isotype diversity of the OVA-specific antibody response, and the proliferation of T lymphocytes. These porins also had adjuvant effects on the antibody response when co-immunized with either the Vi capsular antigen from S. Typhi or inactivated 2009 pandemic influenza A(H1N1) virus [A(H1N1)pdm09]. Taken together, the data indicate that OmpS1 and OmpS2, despite being expressed at low levels under in vitro culture conditions, are potent protective immunogens with intrinsic adjuvant properties. PMID:23432484

  19. The membrane-associated form of α(s1)-casein interacts with cholesterol-rich detergent-resistant microdomains.

    PubMed

    Le Parc, Annabelle; Honvo Houéto, Edith; Pigat, Natascha; Chat, Sophie; Leonil, Joëlle; Chanat, Eric

    2014-01-01

    Caseins, the main milk proteins, interact with colloidal calcium phosphate to form the casein micelle. The mesostructure of this supramolecular assembly markedly influences its nutritional and technological functionalities. However, its detailed molecular organization and the cellular mechanisms involved in its biogenesis have been only partially established. There is a growing body of evidence to support the concept that α(s1)-casein takes center stage in casein micelle building and transport in the secretory pathway of mammary epithelial cells. Here we have investigated the membrane-associated form of α(s1)-casein in rat mammary epithelial cells. Using metabolic labelling we show that α(s1)-casein becomes associated with membranes at the level of the endoplasmic reticulum, with no subsequent increase at the level of the Golgi apparatus. From morphological and biochemical data, it appears that caseins are in a tight relationship with membranes throughout the secretory pathway. On the other hand, we have observed that the membrane-associated form of α(s1)-casein co-purified with detergent-resistant membranes. It was poorly solubilised by Tween 20, partially insoluble in Lubrol WX, and substantially insoluble in Triton X-100. Finally, we found that cholesterol depletion results in the release of the membrane-associated form of α(s1)-casein. These experiments reveal that the insolubility of α(s1)-casein reflects its partial association with a cholesterol-rich detergent-resistant microdomain. We propose that the membrane-associated form of α(s1)-casein interacts with the lipid microdomain, or lipid raft, that forms within the membranes of the endoplasmic reticulum, for efficient forward transport and sorting in the secretory pathway of mammary epithelial cells. PMID:25549363

  20. Picosecond kinetics and Sn <-- S1 absorption spectra of retinoids and carotenoids

    NASA Astrophysics Data System (ADS)

    Bondarev, Stanislav L.; Tikhomirov, S. A.; Bachilo, Sergei M.

    1991-05-01

    Light energy absorption, as well as the subsequent photochemical and photophysical processes of cis -+trans isomerisation (vision and bacteriorhodopsin photosynthesis) and energy transfer (photosynthesis in green plants and micro organisms) take place in a pigment-protein complex including polyene chromophors, retinoids and carotenoids. Picosecond and subpicosecond studies of the spectral and kinetic characteristics of these processes are carried out in both complex photoreceptor and photosynthetic ms'2 and model systems with the use of solutions of retinoids and carotenoids.36 The lifetimes of the lower singlet-exited states S (21A; ) ofsome carotenoids in toluene at room temperature have been measured by the method of picosecond photolysis and amount to 8.6+/- 0.5 for all-trans-fl -carotene1 and 5.2 0.6 PS for canthaxanthin.5 /3 -carotene fluorescence at room temperature is practically absent, its yield being less than iO (Ref. 7). /1 -carotene fluorescence at 77 and 4.2 K in isopentane discovered by us8 is characterized by yields of (4+/-2) .iO and (8+/-3) . i0- and lifetimes of(4+/-2) .iO' and (8+/-3) .iO' and is due to the transitions from the higher S(1' B) state. The picosecond transient S -S absorption of/I - carotene in different solvents at 293 K is characterized by spectra in the 550-600 nm range.8 For retinoids, there is one work (Ref. 4) which gives the S, +-Si absorption spectrum of the Schiff base (aldimine) of retinal with amaz 465 mn in n-hexane at 290 K. The duration of transient absorption was 21 5 ps, although the fluorescence kinetics measured in this work (Ref. 4) at 298 K were characterized by two-component decay with r1 = 22 and r2 = 265 ps. The transient picosecond absorption spectra for retinal are absent in the literature and the lifetimes of its singlet-excited state at room temperature, measured by absorption and fluorescence, amount to 20+/-10 Ps in n-hexane3 and 17 Ps in ethanol,'9 respectively.

  1. The Anomalous Drift of Comet ISON (C/2012 S1) due to Sublimating Volatiles near Perihelion

    NASA Astrophysics Data System (ADS)

    Steckloff, J. K.; Keane, J. V.; Milam, S.; Coulson, I.; Knight, M. M.

    2014-12-01

    Prior to perihelion passage on 28 November 2013, the observed right ascension (RA) and declination (Dec) coordinates of comet C/2012 S1 (ISON) significantly lagged the predicted JPL (# 53) ephemeris. We show that this "braking effect" is due to a dynamic pressure exerted by sublimating gases on the sunward side of the nucleus [1]. Comet ISON was observed November 23 through November 28 using the SCUBA-2 sub-millimeter camera on the James Clerk Maxwell Telescope (JCMT). Imaging is achieved simultaneously at wavelengths of 850 μm and 450 μm, with RA and Dec determined from the central peak in the coma brightness [2]. When comet ISON was first detected at 850 μm, the 1-mm-sized dust particles were tightly bound to the comet nucleus until at least November 23. Three days later, the dust was less tightly bound, elongated and diffuse, spread out over as much as 120 arc seconds (80,000 km) in the anti-solar direction, suggesting a fragmentation event. We compute the average braking velocity of the nucleus of comet ISON by first measuring the distance between the central RA position and the predicted JPL ephemeris. We then calculate the change in this distance between subsequent observations, and divide this value by the elapsed time between the two observations to yield an average drift velocity of the nucleus over this time interval. We assume that comet ISON, like a number of Jupiter Family Comets visited by spacecraft [3], has low thermal inertia. Thus, the sublimating gases are emitted predominantly on the sunward side of the nucleus. Additionally, we assume that water ice dominates the sublimating gases [4]. We then calculate the pressure on the surface of the nucleus due to the emitted gases using the procedure described in [1]. We match the average drift velocity of the nucleus due to this sublimation pressure with the observed average drift velocity from the JCMT observations, which is sensitive to the size of the body, allowing us to estimate the size of the

  2. Observations of comet ISON (C/2012 S1) from Lowell observatory

    SciTech Connect

    Knight, Matthew M.; Schleicher, David G.

    2015-01-01

    We observed the dynamically new sungrazing comet ISON (C/2012 S1) extensively at Lowell Observatory throughout 2013 in order to characterize its behavior prior to perihelion. ISON had “typical” abundances for an Oort Cloud comet. Its dust production, as measured by Afρ, remained nearly constant during the apparition but its CN gas production increased by ∼50 ×. The minimum active area necessary to support observed water production rates exceeded the likely surface area of the nucleus and suggests a population of icy grains in the coma. Together with the flattening of the dust radial profile over time, this is consistant with ejection of a large quantity of slow moving dust and icy grains in the coma at large heliocentric distance. The dust morphology was dominated by the tail, but a faint sunward dust fan was detected in March, April, May, and September. We imaged multiple gas species in September, October, and November. All gas species were more extended than the dust coma, although only CN had sufficient signal-to-noise for detailed morphological study. Excess CN signal was observed in the sunward hemisphere in September and early October. In November the excess CN signal was in the tailward hemisphere and two faint CN features appeared approximately orthogonal to the tail with position angles varying by about ±20° from night to night. Using numerical modeling, we best reproduced the orientation and shape of these features as well as the bulk brightness with a pole oriented approximately toward the Sun and a single source located within ∼35° of the equator. Variations in position angle and relative brightness of the CN features from night to night suggest a rotation period shorter than 24 hr. The production rates and coma morphology suggest a nucleus that was active over nearly its entire sunward facing hemisphere in September and October but which underwent a significant mass loss event, potentially including fragmentation, shortly before November 1

  3. Coma in Comet C/2012 S1 (ISON) at ~4 au

    NASA Astrophysics Data System (ADS)

    Videen, Gorden; Zubko, Evgenij; Hines, Dean C.; Shkuratov, Yuriy; Kaydash, Vadym; Muinonen, Karri; Knight, Matthew W.; Sitko, Michael L.; Lisse, Carrey M.; Mutchler, Max; Wooden, Diane H.; Li, Jian-Yang; Kobayashi, Hiroshi

    2015-11-01

    We analyze HST observations of Comet ISON (C/2012 S1) at heliocentric distance ~4 au and phase angle ~12-14 degree. The inner coma (< 5000 km) reveals two polarimetric features, positive degree of linear polarization P = (2.48 ± 0.45)% at projected distances less than 236 km and negative polarization P = - (1.6 ± 0.45)% at 1000 - 5000 km [Hines et al. 2014: ApJL 780, L32]. At these projected distances, average color slope was found to be ~6% per 100 nm [Li et al. 2013: ApJL 779, L3]. When considered simultaneously, these two features place significant constraint on the physical and chemical properties of dust particles [Zubko et al. 2015: Planet. Space Sci., http://dx.doi.org/10.1016/j.pss.2015.08.002].We model this response with agglomerated debris particles, having highly irregular morphology and density of constituent material being consistent with in situ studies of comets. We consider particles of 28 different refractive indices that correspond to in situ studies of comets and plausible assumptions on chemical composition of cometary dust and ices. What emerges from our analysis is that the ISON coma was chemically heterogeneous at the epoch of observation. The positive polarization at small projected distances suggests a high spatial concentration of highly absorbing materials, such as amorphous carbon and/or organics highly irradiated with UV radiation. At larger distances, the negative polarization P = - (1.6 ± 0.45)% and color slope ~6% per 100 nm appear consistent with organics slightly processed with UV radiation, tholins, Mg-Fe silicates, and Mg-rich silicates contaminated with ~10% (by volume) amorphous carbon. A significant abundance of pure water-ice particles and/or pure Mg-rich silicates must be ruled out in this region. These materials have been found in situ in other comets and also detected with imaging polarimetry in the circumnucleus halo regions. Analyses of polarimetric images suggest that Mg-rich silicates could originate from a

  4. Observations of Comet ISON (C/2012 S1) from Lowell Observatory

    NASA Astrophysics Data System (ADS)

    Knight, Matthew M.; Schleicher, David G.

    2015-01-01

    We observed the dynamically new sungrazing comet ISON (C/2012 S1) extensively at Lowell Observatory throughout 2013 in order to characterize its behavior prior to perihelion. ISON had “typical” abundances for an Oort Cloud comet. Its dust production, as measured by Afρ , remained nearly constant during the apparition but its CN gas production increased by ˜50 ×. The minimum active area necessary to support observed water production rates exceeded the likely surface area of the nucleus and suggests a population of icy grains in the coma. Together with the flattening of the dust radial profile over time, this is consistant with ejection of a large quantity of slow moving dust and icy grains in the coma at large heliocentric distance. The dust morphology was dominated by the tail, but a faint sunward dust fan was detected in March, April, May, and September. We imaged multiple gas species in September, October, and November. All gas species were more extended than the dust coma, although only CN had sufficient signal-to-noise for detailed morphological study. Excess CN signal was observed in the sunward hemisphere in September and early October. In November the excess CN signal was in the tailward hemisphere and two faint CN features appeared approximately orthogonal to the tail with position angles varying by about ±20° from night to night. Using numerical modeling, we best reproduced the orientation and shape of these features as well as the bulk brightness with a pole oriented approximately toward the Sun and a single source located within ˜35° of the equator. Variations in position angle and relative brightness of the CN features from night to night suggest a rotation period shorter than 24 hr. The production rates and coma morphology suggest a nucleus that was active over nearly its entire sunward facing hemisphere in September and October but which underwent a significant mass loss event, potentially including fragmentation, shortly before November 1

  5. Pre-perihelion characterization of Comet C/2012 S1 (ISON)

    NASA Astrophysics Data System (ADS)

    Li, J.; Kelley, M. S.; Farnham, T. L.; A'Hearn, M. F.; Knight, M. M.; Weaver, H. A.; Mutchler, M.; Lamy, P. L.; Toth, I.

    2013-12-01

    Comet C/2012 S1 (ISON) is a dynamically new comet on a sungrazing orbit. As such, C/ISON represents a unique opportunity to study both the cosmic-ray-irradiated surface, produced during the comet's long residence in the Oort cloud, and much deeper layers in the nucleus, exposed when the comet passes within 2 solar radii of the Sun at perihelion. During the first phase of our investigation, we collected broadband images of C/ISON on April 10, 2012 at a heliocentric distance of 4.15 AU, using the Hubble Space Telescope WFC3/UVIS. We used the F606W and F438W filters in three HST orbits covering a total span of ~19 hrs. The comet shows a well delineated coma in the sunward direction extending about 2" from the nucleus, and a dust tail at least 25" long. The coma has an average red color of 5%/0.1 micron within 1.6" from the nucleus, becoming redder towards the tail. Both the color and the size of the coma in the sunward direction are consistent with outflow of micron sized dust. Broadband photometry yielded Afρ of 1376 cm at 589 nm, and 1281 cm at 433 nm, measured with a 1.6" radius aperture. The total brightness of the comet within a 0.12" radius aperture remained unchanged within 0.03 mag for the entire duration of the observations. A well defined sunward jet is visible after removing the 1/ρ brightness distribution. The jet is centered at position angle 290 deg (E of Celestial N), with a cone angle of 45 deg, a projected length of 1.6", and a slight curvature towards the north near the end. No temporal change in the morphology is observed, suggesting the jet is circumpolar. Under this assumption, the jet's apparent position constrains the rotational pole to lie within 30 deg of (RA, Dec) = (330, 0), and an obliquity of 50-80 deg. Preliminary analysis using a coma-nucleus separation technique suggests a nuclear radius less than 2 km. The survival of such a small nucleus during its perihelion at 2.7 solar radii is certainly questionable.

  6. Mid-infrared Observation of C/2012 S1 (ISON) with Subaru+COMCIS

    NASA Astrophysics Data System (ADS)

    Ootsubo, T.; Watanabe, J.; Honda, M.; Yanamandra-Fisher, P. A.; Usui, F.; Takita, S.; Kasuga, T.; Furusho, R.; Fuse, T.; Nagashima, M.; Kawakita, H.; Fujiyoshi, T.

    2013-12-01

    Dust grains in comets have been used to investigate the formation conditions of the solar system. A silicate feature is often observed in comets as a 10-micron resonant feature. In most cases the feature shows the existence of crystalline silicate together with amorphous silicate. Since the crystalline silicate grains are generally made through high-temperature annealing above 800K from amorphous ones, it is believed that the crystalline silicate grains produced at the inner part of the disk were transported to the outer cold regions where comet nuclei formed. Comet C/2012 S1 (ISON) is a long-period Oort cloud comet, discovered in September 2012. Mid-IR observations of this new comet and investigation of the 10-micron silicate feature help us to understand the formation of crystalline silicate grains in the early solar nebula. In particular, comet ISON is a sungrazing comet, which is predicted to pass close by the Sun and Earth and becoming a bright object. We might expect possible splitting and exposing of pristine materials inside the nucleus after its perihelion passage. If it splits, we can also investigate the homogeneity of the comet nucleus, and can compare the results with ecliptic comets, such as 9P/Temple and 73P/SW. Even if it does not split, we can fully investigate the evolution of crystalline grains described above. Thus, observations both at pre- and post-pelihelion are indespensable. We have a plan to observe the comet ISON with COMICS (Cooled Mid-Infrared Camera and Spectrometer) mounted on the 8.2m Subaru Telescope on late October 2013 and mid-January 2014. Subaru+COMICS in mid-infrared is a powerful tool for spectroscopic observations of cometary silicate grains. COMICS observations occupy an important place among organized many facilities and science of comet observations. We will conduct imaging and low-dispersion spectroscopic observations in mid-infrared region for the comet. We will show the preliminary result of the observations on October

  7. Mid-infrared observations of sungrazing comet C/2012 S1 (ISON) with the Subaru Telescope

    NASA Astrophysics Data System (ADS)

    Ootsubo, T.; Usui, F.; Takita, S.; Watanabe, J.; Yanamandra-Fisher, P.; Honda, M.; Kawakita, H.; Furusho, R.

    2014-07-01

    Comets are the frozen reservoirs of the early solar nebula and are made of ice and dust. The determination of the properties for cometary dust provides us insight into both the early-solar-nebula environment and the formation process of the planetary system. A silicate feature is often observed in comet spectra in the mid-infrared region and may be used for probing the early history of the solar system. In most cases, the feature shows the existence of crystalline silicate (for example, 11.3 microns) together with amorphous silicate [1,2]. Since the crystallization of silicates from amorphous ones generally requires high-temperature annealing above 800 K (e.g., [3,4]), it is believed that the crystalline silicate grains produced at the inner part of the disk were transported to the outer cold regions where the comet nuclei formed. Comet C/2012 S1 (ISON) is a long-period Oort Cloud comet, discovered in September 2012. In particular, comet ISON is a sungrazing comet, which was predicted to pass close by the Sun and the Earth and becoming a bright object. Mid-infrared observations of this new comet and investigation of the 10-micron silicate feature help us understand the formation of crystalline silicate grains in the early solar nebula. We conducted observations of comet ISON in the mid-infrared wavelength region with the Cooled Mid-Infrared Camera and Spectrometer (COMICS) on the Subaru Telescope on Mauna Kea, Hawaii [5,6,7]. The observation of comet ISON was carried out on 2013 October 19 and 21 UT. Since the weather conditions were not so good when we observed, we carried out N-band imaging observations (8.8 and 12.4 microns) and N-band low-resolution spectroscopy. The spectrum of comet ISON can be fit with the 260--265-K blackbody spectrum when we use the regions of 7.8--8.2 and 12.4--13.0 microns as the continuum. The spectrum has only a weak silicate excess feature, which may be able to attribute to small amorphous olivine grains. We could not detect a clear

  8. [S1 guideline on the "diagnosis and treatment of snoring in adults"].

    PubMed

    Stuck, B A; Abrams, J; de la Chaux, R; Dreher, A; Heiser, C; Hohenhorst, W; Kühnel, T; Maurer, J T; Pirsig, W; Steffen, A; Verse, T

    2010-03-01

    Due to the frequency of this phenomenon and the often considerable distress caused to the affected person, competent advice, diagnosis and treatment of snoring in adults is of particular importance. The aim of this guideline is to promote high-quality medical care for patients affected by this problem. According to the three-level concept of the AWMF, it corresponds to an S1 guideline. Prior to any therapeutic intervention, relevant sleep medical history, clinical examination, as well as a mandatory objective diagnostic measure are performed. Snoring is only treated if the patient asks for it. In general, invasive methods should be viewed critically and the patient should be advised correspondingly. In the case of surgical therapy, minimally invasive techniques are preferred. Reducing body weight (in the case of overweight snorers), abstinence from alcohol, nicotine and sleep medication, as well as maintaining a healthy sleep-wake cycle can be recommended from a sleep-medicine perspective, although convincing clinical studies are not yet available. Since evidence for the effectiveness of muscle stimulation or various methods for toning and training of the muscles of the floor of mouth is not available, these methods are not recommended. Snoring can be successfully treated with the use of an intraoral device; however, careful patient selection is important. Avoiding a supine position during sleep can be helpful in some cases. Only limited data is available on the success rates of the surgical approaches and long term data is often lacking, and not all techniques have been sufficiently evaluated from a scientific point of view. Nasal surgery is only indicated if the patient suffers from nasal obstruction. Extensive data supports the effectiveness of laser-assisted resection of excessive soft palate tissue (laser-assisted uvuloplasty, LAUP). In principle, however, such resections can be performed using other techniques. Placebo-controlled studies were able to prove

  9. LHC constraints and prospects for S1 scalar leptoquark explaining the B ¯→D(*)τ ν ¯ anomaly

    NASA Astrophysics Data System (ADS)

    Dumont, Béranger; Nishiwaki, Kenji; Watanabe, Ryoutaro

    2016-08-01

    Recently, deviations in flavor observables of B ¯→D(*)τ ν ¯ have been shown between the predictions in the Standard Model and the experimental results reported by BABAR, Belle, and LHCb collaborations. One of the solutions to this anomaly is obtained in a class of leptoquark model with a scalar leptoquark boson S1, which is a S U (3 )c triplet and S U (2 )L singlet particle with -1 /3 hypercharge interacting with a quark-lepton pair. With well-adjusted couplings, this model can explain the anomaly and be compatible with all flavor constraints. In such a case, the S1 boson can be pair-produced at CERN's Large Hadron Collider (LHC) and subsequently decay as S1*→t τ , b ντ, and c τ . This paper explores the current 8 and 13 TeV constraints, as well as the detailed prospects at 14 TeV, of this flavor-motivated S1 model. From the current available 8 and 13 TeV LHC searches, we obtain constraints on the S1 boson mass for MS1<400 - 640 GeV depending on values of the leptoquark couplings to fermions. Then we study future prospects for this scenario at the 14 TeV LHC using detailed cut analyses and evaluate exclusion and discovery potentials for the flavor-motivated S1 leptoquark model from searches for the (b ν )(b ¯ν ¯) and (c τ )(c ¯τ ¯) final states. In the latter case, we consider several scenarios for the identification of charm jets. As a result, we find that the S1 leptoquark origin of the B ¯→D(*)τ ν ¯ anomaly can be probed with MS1≲600 /800 GeV at the 14 TeV LHC with L =300 /3000 fb-1 of accumulated data. One can also see that the 14 TeV LHC run II with L =300 fb-1 can exclude the S1 leptoquark boson up to MS1˜0.8TeV at 95% confidence level, whereas a future 14 TeV LHC with L =3000 fb-1 data has a potential to discover the S1 leptoquark boson with its mass up to MS 1˜1.1 TeV with over 5 σ significance, from the (b ν )(b ¯ν ¯) and/or (c τ )(c ¯τ ¯) searches.

  10. DMRG Study of the S >= 1 quantum Heisenberg Antiferromagnet on a Kagome-like lattice without loops

    NASA Astrophysics Data System (ADS)

    Lamberty, R. Zach; Changlani, Hitesh J.; Henley, Christopher L.

    2013-03-01

    The Kagome quantum Heisenberg antiferromagnet, for spin up to S = 1 and perhaps S = 3 / 2 , is a prime candidate to realize a quantum spin liquid or valence bond crystal state, but theoretical or computational studies for S > 1 / 2 are difficult and few. We consider instead the same interactions and S >= 1 on the Husimi Cactus, a graph of corner sharing triangles whose centers are vertices of a Bethe lattice, using a DMRG procedure tailored for tree graphs. Since both lattices are locally identical, properties of the Kagome antiferromagnet dominated by nearest-neighbor spin correlations should also be exhibited on the Cactus, whereas loop-dependent effects will be absent on the loopless Cactus. Our study focuses on the possible transition(s) that must occur with increasing S for the Cactus antiferromagnet. (It has a disordered valence bond state at S = 1 / 2 but a 3-sublattice coplanar ordered state in the large S limit). We also investigate the phase diagram of the S = 1 quantum XXZ model with on-site anisotropy, which we expect to have three-sublattice and valence-bond-crystal phases similar to the kagome case. This work is supported by the National Science Foundation through a Graduate Research Fellowship to R. Zach Lamberty, as well as grant DMR-

  11. S1PR2 variants associated with auditory function in humans and endocochlear potential decline in mouse.

    PubMed

    Ingham, Neil J; Carlisle, Francesca; Pearson, Selina; Lewis, Morag A; Buniello, Annalisa; Chen, Jing; Isaacson, Rivka L; Pass, Johanna; White, Jacqueline K; Dawson, Sally J; Steel, Karen P

    2016-01-01

    Progressive hearing loss is very common in the population but we still know little about the underlying pathology. A new spontaneous mouse mutation (stonedeaf, stdf ) leading to recessive, early-onset progressive hearing loss was detected and exome sequencing revealed a Thr289Arg substitution in Sphingosine-1-Phosphate Receptor-2 (S1pr2). Mutants aged 2 weeks had normal hearing sensitivity, but at 4 weeks most showed variable degrees of hearing impairment, which became severe or profound in all mutants by 14 weeks. Endocochlear potential (EP) was normal at 2 weeks old but was reduced by 4 and 8 weeks old in mutants, and the stria vascularis, which generates the EP, showed degenerative changes. Three independent mouse knockout alleles of S1pr2 have been described previously, but this is the first time that a reduced EP has been reported. Genomic markers close to the human S1PR2 gene were significantly associated with auditory thresholds in the 1958 British Birth Cohort (n = 6099), suggesting involvement of S1P signalling in human hearing loss. The finding of early onset loss of EP gives new mechanistic insight into the disease process and suggests that therapies for humans with hearing loss due to S1P signalling defects need to target strial function. PMID:27383011

  12. Continuation maintenance therapy with S-1 in chemotherapy-naïve patients with advanced squamous cell lung cancer.

    PubMed

    Suzuki, Seiichiro; Karayama, Masato; Inui, Naoki; Fujisawa, Tomoyuki; Enomoto, Noriyuki; Nakamura, Yutaro; Kuroishi, Shigeki; Matsuda, Hiroyuki; Yokomura, Koshi; Koshimizu, Naoki; Toyoshima, Mikio; Imokawa, Shiro; Asada, Kazuhiro; Masuda, Masafumi; Yamada, Takashi; Watanabe, Hiroshi; Suda, Takafumi

    2016-08-01

    Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer. PMID:27279143

  13. A non-adiabatic dynamics study of octatetraene: the radiationless conversion from S2 to S1.

    PubMed

    Qu, Zexing; Liu, Chungen

    2013-12-28

    Simulation of the excited state dynamics of all-trans-1,3,5,7-octatetraene has been performed to investigate the ultrafast radiationless S2 → S1 internal conversion process. Multireference configuration interaction with single excitation method has been employed to optimize the equilibrium structure of the excited states, as well as the S2/S1 conical intersection, and to investigate the non-adiabatic molecular dynamics of the S2/S1 state transition. At the conical intersection, the molecule is found to be distorted from the original planar trans structure to a nearly perpendicular conformation around C3-C4 bond, with the torsion angle being about 107°. Such structural change can result in mutual approaching of states S2 and S1 in energy, and drastically increase the nonadiabatic coupling between the two states by destroying the inter-state symmetry prohibition in the electronic wavefunctions. Surface-hopping molecular dynamics simulations are performed to describe the non-adiabatic process. Upon the Franck-Condon excitation to the S2 state, the molecule quickly twists its C3-C4 bond and approaches the conical intersection region, where it can undergo efficient internal conversion to S1. The decay time constant (τ) of S2 state is estimated to be around 251 fs by fitting the occupation number of average fraction of trajectories using an exponential damping function. This value is reasonably consistent with previous experimental measurements of around 300-400 fs. PMID:24387367

  14. L-leucine transport systems in Saccharomyces cerevisiae participation of GAP1, S1 and S2 transport systems.

    PubMed

    Kotliar, N; Stella, C A; Ramos, E H; Mattoon, J R

    1994-09-01

    L-leucine uptake in Saccharomyces cerevisiae is mediated by three different transport systems, S1, S2 and GAP1. Their activities are dependent on the nitrogen source of the culture media. Wild type cells grown in L-proline exhibit a single transport system with high affinity and high Vmax that is partially inhibited by L-citrulline. A gap1 mutant shows two transport systems with Km and Vmax values similar to those previously described as S1 and S2, this transport activity is not inhibited by D-leucine, D-isoleucine or D-valine. Two systems can be also determined in wild type cells grown in rich medium containing a mixed nitrogen source where decreased GAP1 function is observed. In either wild type or gap1 cells grown in medium containing ammonium ions as sole nitrogen source, L-leucine uptake kinetics shows two systems with lower Vmax and similar Km values to those of the S1 and S2 systems. These results show that in S. cerevisiae GAP1, S1 and S2 participate in L-leucine entrance in cells grown in a poor nitrogen source, and that S1 and S2 are two ammonia-sensitive permeases that mediate the uptake in cells grown in a rich nitrogen source. PMID:7812191

  15. Anti-proliferative and apoptotic effects of S1, a tetrandrine derivative, in human gastric cancer BGC-823 cells.

    PubMed

    Lei, Rong-Rong; Hu, Hai-Feng; Bai, Fan; Liu, Ying; Wu, Chun-Zhen; Huang, Xiao-Xing; Xie, Li-Ping; Hu, You-Jia

    2016-07-01

    The aim of the study was to investigate the anti-proliferation and apoptosis-inducing effects of S1, a novel tetrandrine derivative, in human gastric cancer BGC-823 cells and explore the possible mechanism of action. The anti-proliferative activity was determined by MTT assay; the induction of cell cycle arrest and apoptosis were detected by flow cytometry. Quantitative real time RT-PCR and Western blotting were used to evaluate the mRNA and protein expression levels in mitochondrial pathway. S1 significantly reduced cell viability and induced a G2/M phase arrest and apoptosis in dose- and time-dependent manner. Further studies showed that S1 increased mRNA and protein expression of Bax and the Bax/Bcl-2 ratio. Moreover, S1 decreased the protein expression of procaspase-9 and procaspase-3, suggesting that the induction of apoptosis may be related to the alteration of the ratio of Bax/Bcl-2 and the activation of caspases. These findings suggested that S1 merits further investigation as a novel therapeutic agent for the treatment of human gastric cancer. PMID:27507203

  16. S1PR2 variants associated with auditory function in humans and endocochlear potential decline in mouse

    PubMed Central

    Ingham, Neil J.; Carlisle, Francesca; Pearson, Selina; Lewis, Morag A.; Buniello, Annalisa; Chen, Jing; Isaacson, Rivka L.; Pass, Johanna; White, Jacqueline K.; Dawson, Sally J.; Steel, Karen P.

    2016-01-01

    Progressive hearing loss is very common in the population but we still know little about the underlying pathology. A new spontaneous mouse mutation (stonedeaf, stdf ) leading to recessive, early-onset progressive hearing loss was detected and exome sequencing revealed a Thr289Arg substitution in Sphingosine-1-Phosphate Receptor-2 (S1pr2). Mutants aged 2 weeks had normal hearing sensitivity, but at 4 weeks most showed variable degrees of hearing impairment, which became severe or profound in all mutants by 14 weeks. Endocochlear potential (EP) was normal at 2 weeks old but was reduced by 4 and 8 weeks old in mutants, and the stria vascularis, which generates the EP, showed degenerative changes. Three independent mouse knockout alleles of S1pr2 have been described previously, but this is the first time that a reduced EP has been reported. Genomic markers close to the human S1PR2 gene were significantly associated with auditory thresholds in the 1958 British Birth Cohort (n = 6099), suggesting involvement of S1P signalling in human hearing loss. The finding of early onset loss of EP gives new mechanistic insight into the disease process and suggests that therapies for humans with hearing loss due to S1P signalling defects need to target strial function. PMID:27383011

  17. Phenytoin toxicity in a patient receiving concomitant use of phenytoin and S-1 plus cisplatin chemotherapy for advanced gastric cancer.

    PubMed

    Mimatsu, Kenji; Oida, Takatsugu; Kawasaki, Atsushi; Kida, Kazutoshi; Fukino, Nobutada; Kuboi, Youichi; Kano, Hisao; Amano, Sadao

    2011-06-01

    A 61-year-old man had been receiving phenytoin(225mg/day)and valproate(600mg/day)for several years as the treatment for seizures. He was diagnosed with advanced gastric cancer,and S-1 plus cisplatin treatment was administered as neoadjuvant chemotherapy because bulky lymph node metastases were found at the time of the initial diagnosis. He complained of weakness of the lower extremities,light -headedness,and trembling of the upper extremities 2 months after the start of concomitant treatment with S-1 plus cisplatin. The serum phenytoin concentration increased to 21. 2mg/mL. Head computed tomography and magnetic resonance imaging did not reveal any intracranial lesion such as brain metastasis. Therefore, we diagnosed phenytoin toxicity due to concomitant use of S-1 and phenytoin,and the dose of phenytoin was then decreased to 150 mg. Although the weakness of the lower extremities improved,light -headedness remained. Phenytoin and valproate treatments were stopped,and he was able to walk 7 days after the termination of therapy. It is important to predict the timing of phenytoin toxicity due to S-1,and therapeutic drug monitoring should be performed in patients receiving S-1 plus cisplatin and phenytoin. PMID:21677496

  18. Phase I study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer

    SciTech Connect

    Sudo, Kentaro; Yamaguchi, Taketo . E-mail: yama.take@faculty.chiba-u.jp; Ishihara, Takeshi; Nakamura, Kazuyoshi; Shirai, Yoshihiko; Nakagawa, Akihiko; Kawakami, Hiroyuki; Uno, Takashi; Ito, Hisao; Saisho, Hiromitsu

    2007-01-01

    Purpose: The primary objective of this study was to determine the maximum-tolerated dose (MTD) of S-1, an oral fluoropyrimidine derivative, with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Methods and Materials: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day from Day 1 to 14 and 22 to 35 at escalating doses from 60 to 80 mg/m{sup 2}/day. Results: Sixteen patients were enrolled in this study. Three patients received S-1 at 60 mg/m{sup 2}/day, 3 at 70 mg/m{sup 2}/day, and 10 at 80 mg/m{sup 2}/day. Though 1 patient at the final dose level (80 mg/m{sup 2}/day) experienced a dose limiting toxicity (biliary infection with Grade 3 neutropenia), the MTD was not reached in this study. The most common toxicities were anorexia and leukocytopenia, with Grade 3 toxicity occurring in 31% and 6.3% of the patients, respectively. Conclusions: The recommended dose of S-1 with concurrent radiotherapy was determined to be 80 mg/m{sup 2}/day from Day 1 to 14 and 22 to 35 in patients with locally advanced pancreatic cancer. Oral S-1 and radiotherapy is well tolerated and feasible and should be further investigated.

  19. Are Boltzmann plots of hydrogen Balmer lines a tool for identifying a subclass of S1 AGN?

    NASA Astrophysics Data System (ADS)

    Rafanelli, P.; Ciroi, S.; Cracco, V.; Di Mille, F.; Ilić, D.; La Mura, G.; Popović, L. Č.

    2014-10-01

    It is becoming clear that we can define two different types of nearby AGN belonging to the Seyfert 1 class (S1), on the basis of the match of the intensities of their Broad Balmer Lines (BBL) with the Boltzmann Plots (BP). These two types of S1 galaxies, that we call BP-S1 and NoBP-S1, are characterized, in first approximation, by Broad Line Regions (BLR) with different structural and physical properties. In this communication, we show that these features can be well pointed out by a multi-wavelength analysis of the continuum and of the broad recombination Hydrogen lines, that we carry out on a sample of objects detected at optical and X-ray frequencies. The investigation is addressed to verify whether BP-S1 are the ideal candidates for the study of the kinematical and structural properties of the BLR, in order to derive reliable estimates of the mass of their central engine and to constrain the properties of their nuclear continuum spectrum.

  20. Localization of cytochrome P450 CYP2S1 expression in human tissues by in situ hybridization and immunohistochemistry.

    PubMed

    Saarikoski, Sirkku T; Wikman, Harriet A-L; Smith, Gillian; Wolff, C Henrik J; Husgafvel-Pursiainen, Kirsti

    2005-05-01

    CYP2S1 is a recently discovered dioxin-inducible member of the cytochrome P450 superfamily. It has been shown to be involved in the metabolism of some aromatic hydrocarbons as well as retinoic acid, suggesting a role in biotransformation of both exogenous and endogenous compounds. In this study, we used mRNA in situ hybridization and immunohistochemistry to investigate the cellular localization of CYP2S1 in various human tissues using tissue microarrays. High expression levels were observed mainly in epithelial cell types, especially in the epithelia frequently exposed to xenobiotics. In the respiratory tract, the expression was strong in nasal cavity, bronchi, and bronchioli, whereas it was low in the alveolar lining cells. Similarly, CYP2S1 was highly expressed in the epithelial cells throughout the gastrointestinal tract. Strong epithelial expression was also observed in uterine cervix, urinary bladder, and skin. In many exocrine glands (e.g., adrenal gland and pancreas), secretory epithelial cells showed moderate to strong expression levels. In the liver, the expression was low. CYP2S1 was highly expressed in epithelial cells that are major targets for carcinogen exposure and common progenitor cells to tumor development. Indeed, we found strong CYP2S1 expression in many tumors of epithelial origin. PMID:15872048

  1. SIRT3 participates in glucose metabolism interruption and apoptosis induced by BH3 mimetic S1 in ovarian cancer cells.

    PubMed

    Xiang, Xi-Yan; Kang, Jin-Song; Yang, Xiao-Chun; Su, Jing; Wu, Yao; Yan, Xiao-Yu; Xue, Ya-Nan; Xu, Ye; Liu, Yu-He; Yu, Chun-Yan; Zhang, Zhi-Chao; Sun, Lian-Kun

    2016-08-01

    The Bcl-2 antiapoptotic proteins are important cancer therapy targets; however, their role in cancer cell metabolism remains unclear. We found that the BH3-only protein mimetic S1, a novel pan Bcl-2 inhibitor, simultaneously interrupted glucose metabolism and induced apoptosis in human SKOV3 ovarian cancer cells, which was related to the activation of SIRT3, a stress-responsive deacetylase. S1 interrupted the cellular glucose metabolism mainly through causing damage to mitochondrial respiration and inhibiting glycolysis. Moreover, S1 upregulated the gene and protein expression of SIRT3, and induced the translocation of SIRT3 from the nucleus to mitochondria. SIRT3 silencing reversed the effects of S1 on glucose metabolism and apoptosis through increasing the level of HK-II localized to the mitochondria, while a combination of the glycolysis inhibitor 2-DG and S1 intensified the cytotoxicity through further upregulation of SIRT3 expression. This study underscores an essential role of SIRT3 in the antitumor effect of Bcl-2 inhibitors in human ovarian cancer through regulating both metabolism and apoptosis. The manipulation of Bcl-2 inhibitors combined with the use of classic glycolysis inhibitors may be rational strategies to improve ovarian cancer therapy. PMID:27277143

  2. Successful curative resection of gallbladder cancer following S-1 chemotherapy: A case report and review of the literature.

    PubMed

    Einama, Takahiro; Uchida, Koichiro; Taniguchi, Masahiko; Ota, Yu; Watanabe, Kenji; Imai, Koji; Karasaki, Hidenori; Chiba, Atsushi; Oikawa, Kensuke; Miyokawa, Naoyuki; Furukawa, Hiroyuki

    2014-12-01

    The symptoms of gallbladder cancer (GBC) are vague and non-specific. Therefore, GBC is often detected at an advanced or metastatic stage. The most effective treatment for GBC is surgical resection, however the majority of GBC cases are unresectable at the time of diagnosis. Therefore, numerous GBC patients undergo chemotherapy. This study reports the case of a 60-year-old female with GBC who underwent successful surgical curative resection following a single dose of the chemotherapeutic agent, S-1, twice daily for 4 weeks followed by a 14-day rest period for 36 months. S-1 is a novel orally administered drug composed of a combination of the 5-fluorouracil (5-FU) prodrug, tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and oteracil potassium in a 1:0.4:1 molar concentration ratio. The focus of the present study was the candidate factors that affect the therapeutic efficacy of S-1-based chemotherapy. In particular, the gene expression involved in the S-1 metabolic pathway was investigated by assessing the intratumoral dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS) and orotate phosphoribosyltransferase gene expression. The surgical specimen exhibited high intratumoral DPD gene expression levels compared with those observed in previously reported non S-1 responsive cases of biliary tract cancer. Due to the results obtained in the current study, we hypothesize that CDHP enhanced the antitumor efficacy of 5-FU by inhibiting the excess DPD protein produced by the tumor. PMID:25360167

  3. Successful curative resection of gallbladder cancer following S-1 chemotherapy: A case report and review of the literature

    PubMed Central

    EINAMA, TAKAHIRO; UCHIDA, KOICHIRO; TANIGUCHI, MASAHIKO; OTA, YU; WATANABE, KENJI; IMAI, KOJI; KARASAKI, HIDENORI; CHIBA, ATSUSHI; OIKAWA, KENSUKE; MIYOKAWA, NAOYUKI; FURUKAWA, HIROYUKI

    2014-01-01

    The symptoms of gallbladder cancer (GBC) are vague and non-specific. Therefore, GBC is often detected at an advanced or metastatic stage. The most effective treatment for GBC is surgical resection, however the majority of GBC cases are unresectable at the time of diagnosis. Therefore, numerous GBC patients undergo chemotherapy. This study reports the case of a 60-year-old female with GBC who underwent successful surgical curative resection following a single dose of the chemotherapeutic agent, S-1, twice daily for 4 weeks followed by a 14-day rest period for 36 months. S-1 is a novel orally administered drug composed of a combination of the 5-fluorouracil (5-FU) prodrug, tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and oteracil potassium in a 1:0.4:1 molar concentration ratio. The focus of the present study was the candidate factors that affect the therapeutic efficacy of S-1-based chemotherapy. In particular, the gene expression involved in the S-1 metabolic pathway was investigated by assessing the intratumoral dihydropyrimidine dehydrogenase (DPD), thymidylate synthase (TS) and orotate phosphoribosyltransferase gene expression. The surgical specimen exhibited high intratumoral DPD gene expression levels compared with those observed in previously reported non S-1 responsive cases of biliary tract cancer. Due to the results obtained in the current study, we hypothesize that CDHP enhanced the antitumor efficacy of 5-FU by inhibiting the excess DPD protein produced by the tumor. PMID:25360167

  4. Design, Synthesis, and In Vitro and In Vivo Evaluation of an (18)F-Labeled Sphingosine 1-Phosphate Receptor 1 (S1P1) PET Tracer.

    PubMed

    Rosenberg, Adam J; Liu, Hui; Jin, Hongjun; Yue, Xuyi; Riley, Sean; Brown, Steven J; Tu, Zhude

    2016-07-14

    Sphingosine 1-phosphate receptor 1 (S1P1) plays a pivotal signaling role in inflammatory response; because S1P1 modulation has been identified as a therapeutic target for various diseases, a PET tracer for S1P1 would be a useful tool. Fourteen fluorine-containing analogues of S1P ligands were synthesized and their in vitro binding potency measured; four had high potency and selectivity for S1P1 (S1P1 IC50 < 10 nM, >100-fold selectivity for S1P1 over S1P2 and S1P3). The most potent ligand, 28c (IC50 = 2.63 nM for S1P1) was (18)F-labeled and evaluated in a mouse model of LPS-induced acute liver injury to determine its S1P1-binding specificity. The results from biodistribution, autoradiography, and microPET imaging showed higher [(18)F]28c accumulation in the liver of LPS-treated mice than controls. Increased expression of S1P1 in the LPS model was confirmed by immunohistochemical analysis (IHC). These data suggest that [(18)F]28c is a S1P1 PET tracer with high potential for imaging S1P1 in vivo. PMID:27280499

  5. Novel alkaline earth copper germanates with ferro and antiferromagnetic S=1/2 chains

    SciTech Connect

    Brandao, Paula; Reis, Mario S.; Santos, Antonio M. dos

    2013-02-15

    Two new alkaline earth copper(II) germanates were hydrothermally synthesized: CaCuGeO{sub 4}{center_dot}H{sub 2}O (1) and BaCu{sub 2}Ge{sub 3}O{sub 9}{center_dot}H{sub 2}O (2), and their structures determined by single crystal X-ray diffraction. Compound (1) crystallizes in space group P2{sub 1}/c with a=5.1320(2) Angstrom-Sign , b=16.1637(5) Angstrom-Sign , c=5.4818(2) Angstrom-Sign , {beta}=102.609(2) Degree-Sign , V=443.76(3) Angstrom-Sign {sup 3} and Z=4. This copper germanate contains layers of composition [CuGeO{sub 4}]{sub {infinity}}{sup 2-} comprising CuO{sub 4} square planes and GeO{sub 4} tetrahedra with calcium and water molecules in the inter-layer space. Compound (2) crystallizes in the Cmcm space group with a=5.5593(3) Angstrom-Sign , b=10.8606(9) Angstrom-Sign , c=13.5409(8) Angstrom-Sign , V=817.56(9) Angstrom-Sign {sup 3} and Z=4. This structure contains GeO{sub 6} and CuO{sub 6} octahedra as well as GeO{sub 4} tetrahedra, forming a three-dimensional network of interconnecting six-membered ring channels. The magnetic susceptibility for both samples can be interpreted as S=1/2 chains, in agreement with the copper topology observed in the crystal structure. The susceptibility of (1) exhibits a Bonner-Fisher type behavior, resulting from antiferromagnetic intra-chain interactions without three-dimensional ordering down to 5 K-the lowest measured temperature. This observation, together with the absence of super-exchange paths between the copper chains, make this system particularly promising for the study of low dimensional magnetism. The magnetic properties of (2) show a very weak ferromagnetic near-neighbor interaction along the chain. In this compound a peak the {chi}T plot seems to indicate the onset of interchain antiferromagentic correlations. However, no ordering temperature is detected in the susceptibility data. - Graphical abstract: Copper chains present in CaCuGeO{sub 4}{center_dot}H{sub 2}O and BaCu{sub 2}Ge{sub 3}O{sub 9}{center

  6. Studies on Structural, Morphological and Optical Properties of Chemically Deposited CdS1-xSex Thin Films.

    PubMed

    Deo, Soumya R; Singh, Ajaya K; Deshmukh, Lata; Singh, Narendra Pratap; Aleksandrova, Mariya P

    2016-03-01

    The thin films of CdS1-xSex were successfully deposited over glass substrates by chemical bath deposition technique. Cadmium acetate, thiourea and sodium selenosulfate were used as source materials for Cd(2+), S(2-) and Se(2-) ions, while 2-mercaptoethanol was used as capping agent. The various deposition conditions such as precursor concentration, deposition temperature, pH and deposition time were optimized for the deposition of CdS1-xSex thin films of good quality and the films were annealed at 200° and 300 °C. The structural, morphological, chemical and optical properties were examined by various characterization techniques and discussed in detail. The optical band gap of CdS1-xSex thin film samples were estimated and found in the range from 2.11 to 1.79 eV for as-deposited and annealed thin films. PMID:26634707

  7. Vibrational spectrum of p-fluoroanisole in the first excited state (S 1) and ab initio calculations

    NASA Astrophysics Data System (ADS)

    Xiao, Daoqing; Yu, Dan; Xu, Xiling; Yu, Zijun; Du, Yikui; Gao, Zhen; Zhu, Qihe; Zhang, Cunhao

    2008-06-01

    The vibronic structure of p-fluoroanisole in the first excited state (S 1) has been investigated with mass selected resonance-enhanced two photon ionization spectroscopy. The band origin of S 1 ← S 0 transition of p-fluoroanisole is measured to be 35149 cm -1, which is red-shifted by 1234 cm -1 with respect to that of anisole. Combining with the ab initio calculations, the measured frequencies 397, 487, 559, 840 and 1150 cm -1 in the S 1 state are assigned as the in-plane ring vibrational mode 9 b, 6 a, 6 b, 1 and 9 a, respectively. The optimized molecular geometries and vibrational frequencies of p-fluoroanisole in the ground state (S 0) and cation ground state (D 0) are also achieved from DFT calculations.

  8. [A Case of Advanced Gastric Cancer with Peritoneal Dissemination Effectively Treated with S-1 and Docetaxel Combination Chemotherapy].

    PubMed

    Saito, Hiroyuki; Suematsu, Yuki; Hiratsuka, Miyuki; Suda, Hiroshi; Takahashi, Miyuki; Omori, Keita; Ishibashi, Yuji; Morita, Akihiko; Wakabayashi, Kazuhiko; Ito, Yutaka

    2015-11-01

    A 72-year-old man underwent surgery for advanced gastric cancer. Systemic chemotherapy was started, using a regimen of S-1/CDDP for 4 courses, followed by 8 courses of S-1. Three years and 8 months after the surgery, abdominal CT demonstrated ascites, and the serum CA19-9 level was abnormally high (1,165.1 U/mL). Adenocarcinoma cells were found in the ascites. Treatment with S-1/docetaxel (DOC) was started. After 10 courses, the ascites disappeared and the serum CA19-9 value returned to normal. Four years and 7 months after the operation, the patient has been in good health, with no signs of recurrence. PMID:26805261

  9. Structure of conkunitzin-S1, a neurotoxin and Kunitz-fold disulfide variant from cone snail

    PubMed Central

    Dy, Catherine Y.; Buczek, Pawel; Imperial, Julita S.; Bulaj, Grzegorz; Horvath, Martin P.

    2006-01-01

    Cone snails (Conus) are predatory marine mollusks that immobilize prey with venom containing 50–200 neurotoxic polypeptides. Most of these polypeptides are small disulfide-rich conotoxins that can be classified into families according to their respective ion-channel targets and patterns of cysteine–cysteine disulfides. Conkunitzin-S1, a potassium-channel pore-blocking toxin isolated from C. striatus venom, is a member of a newly defined conotoxin family with sequence homology to Kunitz-fold proteins such as α-dendrotoxin and bovine pancreatic trypsin inhibitor (BPTI). While conkunitzin-S1 and α-dendrotoxin are 42% identical in amino-acid sequence, conkunitzin-S1 has only four of the six cysteines normally found in Kunitz proteins. Here, the crystal structure of conkunitzin-S1 is reported. Conkunitzin-S1 adopts the canonical 310–β–β–α Kunitz fold complete with additional distinguishing structural features including two completely buried water molecules. The crystal structure, although completely consistent with previously reported NMR distance restraints, provides a greater degree of precision for atomic coordinates, especially for S atoms and buried solvent molecules. The region normally cross-linked by cysteines II and IV in other Kunitz proteins retains a network of hydrogen bonds and van der Waals interactions comparable to those found in α-dendrotoxin and BPTI. In conkunitzin-S1, glycine occupies the sequence position normally reserved for cysteine II and the special steric properties of glycine allow additional van der Waals contacts with the glutamine residue substituting for cysteine IV. Evolution has thus defrayed the cost of losing a disulfide bond by augmenting and optimizing weaker yet nonetheless effective non-covalent interactions. PMID:16929098

  10. [A Case of Recurrent Gallbladder Cancer with a Complete Response to S-1 Alternate-Day Administration].

    PubMed

    Eto, Ryuichi; Nakatsu, Hiroki; Ozasa, Hiroaki; Shimizu, Ryoichi

    2016-01-01

    An 86-year-old woman underwent a cholecystectomy for gallbladder cancer. Seven months later, an abdominal CT scan showed multiple liver and lymph node metastases. Treatment with S-1 was started at a dose of 100 mg/day, but was changed to alternate-day administration because of diarrhea. Metastatic lesions showed a complete response after 7 months of chemotherapy. S-1 alternate-day therapy could be maintained without any severe adverse events. This method can be managed safely and with certainty in an elderly patient and it has demonstrated efficacy in the treatment of recurrent gallbladder cancer. PMID:26809537

  11. Functional Characterization of Human Cytochrome P450 2S1 Using a Synthetic Gene-Expressed Protein in Escherichia coli

    PubMed Central

    Bui, Peter H.

    2009-01-01

    Human cytochrome P450 2S1 was recently identified and shown to be inducible by 2,3,7,8-tetrachlorodibenzo-p-dioxin and hypoxia. It is highly expressed in epithelial cells of tissues that are exposed to the environment and in many tumors of epithelial origin. The biological function of CYP2S1 has not yet been determined, although its possible role in carcinogen metabolism has been suggested. In this report, we investigated its ability to metabolize carcinogens. To obtain a large quantity of active enzyme for substrate screening, we overexpressed CYP2S1 in Escherichia coli (200 nM culture), using a synthetic gene approach. High-level expression allowed us to achieve purification of CYP2S1 with high specific content and purity (16 nmol/mg). Despite high-level expression, we found that CYP2S1 was not readily reduced by cytochrome P450 reductase, and thus no activity was found using NADPH. However, the oxidative activity of CYP2S1 was supported by cumene hydroperoxide or H2O2, such that CYP2S1 oxidized many important environmental carcinogens, including benzo[a]pyrene, 9,10-dihydro-benzo[a]pyrene, 7,12-dimethylbenz[a]anthracene, benzo[a]pyrene-7,8-dihydrodiol, aflatoxin B1, naphthalene, and styrene, with high turnover. Most substrates tested were converted to detoxification products, except in the case of benzo[a]pyrene-7,8-dihydrodiol, which was converted into the very potent carcinogenic metabolite 7,8-dihydrodiol-trans-9,10-epoxide at a relatively efficient rate (Km = 12.4 ± 2 μM, turnover = 2.3 min−1). This metabolite formation was also supported both in vitro and in vivo by fatty acid hydroperoxides described in the accompanying report (p. 1044). Together, these data indicate that CYP2S1 contributes to the metabolism of environmental carcinogens via an NADPH independent activity. PMID:19713358

  12. Phase 1 study on S-1 and oxaliplatin therapy as an adjuvant after hepatectomy for colorectal liver metastases.

    PubMed

    Takahashi, Michiro; Hasegawa, Kiyoshi; Oba, Masaru; Saiura, Akio; Arita, Junichi; Sakamoto, Yoshihiro; Shinozaki, Eiji; Mizunuma, Nobuyuki; Matsuyama, Yutaka; Kokudo, Norihiro

    2016-08-01

    of Background Data The effectiveness of adjuvant chemotherapy in patients with stage II/III colorectal cancer has been confirmed in various studies. However, no adjuvant chemotherapy for colorectal liver metastasis (CLM) classified to stage IV has been established. Objectives We conducted a phase 1 study of S-1 and oxaliplatin to determine the recommended dose (RD) in patients with CLM as adjuvant therapy in two institutes. Methods S-1 and oxaliplatin were administered from day 1 to day 14 of a 3-week cycle as a 2-h infusion every 3 weeks, respectively. The initial doses of S-1 and oxaliplatin were fixed to 80 mg/m(2) and 100 mg/m(2), respectively (level 1). We scheduled in the protocol a dose change of S-1 and oxaliplatin to level 2 (S-1: 80 mg/m(2) and oxaliplatin: 130 mg/m(2)) or level 0 (S-1: 65 mg/m(2) and oxaliplatin: 100 mg/m(2)) depending on the incidence of dose-limiting toxicity (DLT) at level 1 in six patients. Results Because DLT occurred in one among the initial six patients at level 1, the doses were increased to level 2 in the next six patients. At level 2, grade 3 leukopenia and neutropenia occurred in one (16.7 %) and two (33.3 %) patients, respectively, in the absence of non-hematological event. Because no DLT occurred at level 2, we suggest that the RD can be set to the level 2 dose. The median number of cycles delivered at RD was 8. The mean relative dose intensity of S-1 and oxaliplatin at RD was 0.90 and 0.63, respectively. Conclusion In a patient undergoing hepatectomy for CLM, 80 mg/m(2) of S-1 and 130 mg/m(2) of oxaliplatin are recommended as adjuvant therapy. A further study is required to confirm the efficacy and safety of this regimen on a larger scale. PMID:27155613

  13. Measurement of the 3s1/2-3p3/2 resonance line of sodiumlike Eu52+

    DOE PAGESBeta

    Träbert, E.; Beiersdorfer, P.; Hell, N.; Brown, G. V.

    2015-08-20

    We have measured the 3s1/2-3p3/2 transition in sodiumlike Eu52+ situated at 41.232 Å with an uncertainty of 73 ppm. Our measurement extends previous high-precision measurements into the 56< Z< 78 range of atomic numbers. We also present measurements of 3s1/2-3p3/2 and 3p1/2-3d3/2 transitions in the neighboring magnesiumlike, aluminumlike, and siliconlike europium ions.

  14. Synthesis and Properties of the Heterospin (S1 = S2 = (1)/2) Radical-Ion Salt Bis(mesitylene)molybdenum(I) [1,2,5]Thiadiazolo[3,4-c][1,2,5]thiadiazolidyl.

    PubMed

    Pushkarevsky, Nikolay A; Semenov, Nikolay A; Dmitriev, Alexey A; Kuratieva, Natalia V; Bogomyakov, Artem S; Irtegova, Irina G; Vasilieva, Nadezhda V; Bode, Bela E; Gritsan, Nina P; Konstantinova, Lidia S; Woollins, J Derek; Rakitin, Oleg A; Konchenko, Sergey N; Ovcharenko, Victor I; Zibarev, Andrey V

    2015-07-20

    Low-temperature interaction of [1,2,5]thiadiazolo[3,4-c][1,2,5]thiadiazole (1) with MoMes2 (Mes = mesitylene/1,3,5-trimethylbenzene) in tetrahydrofuran gave the heterospin (S1 = S2 = (1)/2) radical-ion salt [MoMes2](+)[1](-) (2) whose structure was confirmed by single-crystal X-ray diffraction (XRD). The structure revealed alternating layers of the cations and anions with the Mes ligands perpendicular, and the anions tilted by 45°, to the layer plane. At 300 K the effective magnetic moment of 2 is equal to 2.40 μB (theoretically expected 2.45 μB) and monotonically decreases with lowering of the temperature. In the temperature range 2-300 K, the molar magnetic susceptibility of 2 is well-described by the Curie-Weiss law with parameters C and θ equal to 0.78 cm(3) K mol(-1) and -31.2 K, respectively. Overall, the magnetic behavior of 2 is similar to that of [CrTol2](+)[1](-) and [CrCp*2](+)[1](-), i.e., changing the cation [MAr2](+) 3d atom M = Cr (Z = 24) with weak spin-orbit coupling (SOC) to a 4d atom M = Mo (Z = 42) with stronger SOC does not affect macroscopic magnetic properties of the salts. For the XRD structure of salt 2, parameters of the Heisenberg spin-Hamiltonian were calculated using the broken-symmetry DFT and CASSCF approaches, and the complex 3D magnetic structure with both the ferromagnetic (FM) and antiferromagnetic (AF) exchange interactions was revealed with the latter as dominating. Salt 2 is thermally unstable and slowly loses the Mes ligands upon storage at ambient temperature. Under the same reaction conditions, interaction of 1 with MoTol2 (Tol = toluene) proceeded with partial loss of the Tol ligands to afford diamagnetic product. PMID:26121418

  15. Anterior Lumbar Interbody Fusion for Degenerative Discogenic Low Back Pain: Evaluation of L4-S1 Fusion.

    PubMed

    Ni, Jianqiang; Fang, Xiutong; Zhong, Weiye; Liu, Ning; Wood, Kirkham B

    2015-10-01

    The treatment of degenerative discogenic pain is controversial, and anterior lumbar fusion for the treatment of degenerative discogenic low back pain has also been a controversial topic for over a generation.The aim of this systematic review was to evaluate the outcome of different anterior lumbar fusion levels for degenerative discogenic low back pain.In this study, we performed a clinical outcome subgroup analysis. The outcomes of 84 consecutive patients who underwent anterior lumbar interbody fusion from 2004 to 2009 were reviewed. The operative time, intraoperative blood loss, hospital stay, Oswestry Disability Index (ODI), visual analog scale (VAS) results, and complication rate were recorded separately.Medical indications were degenerative disc disease (73.8%), postdiscectomy disc disease (16.1%), and disc herniation (9.5%). Patients with severe spondylolysis or disc degeneration, with more than 3 or multilevel lesions, were excluded.The mean operative time was 124.5 ± 10.9 min (range 51-248 min), the mean intraoperative blood loss was 242.1 ± 27.7 mL (range 50-2700 mL), the mean hospital stay was 3.9 ± 1.1 days (range 3-6 days), the mean preoperative VAS score was 7.5 ± 1.4, and the mean preoperative ODI score was 60.0 ± 5.7. At the 1-year follow-up, the mean postoperative VAS score was 3.3 ± 1.3 and the mean postoperative ODI score was 13.6 ± 3.4 (P < 0.05). L4-L5 disc fusion led to better clinical results than 2-level L4-L5/L5-S1 disc fusion. Additionally, the 2-level fusion of L4-L5/L5-S1 had better clinical results than the L5-S1 disc fusion at both the 1 and 2-year postoperative follow-ups regarding the VAS score and the ODI score. The rate of complications was more frequent in the 2-level L4-L5/L5-S1 group (27.3%) (group C) than in the L4-L5 group (9.1%) (group A) and the L5-S1 group (12.5%) (group B). There was no difference between the L4-L5 group (9.1%) and the L5-S1 group (12.5%). A venous tear

  16. S1P activates store-operated calcium entry via receptor- and non-receptor-mediated pathways in vascular smooth muscle cells.

    PubMed

    Hopson, Kristen Park; Truelove, Jessica; Chun, Jerold; Wang, Yumei; Waeber, Christian

    2011-04-01

    Sphingosine-1-phosphate (S1P) has been shown to modulate intracellular Ca(2+) through both G protein-coupled receptors and intracellular second messenger pathways. The precise mechanism by which S1P activates store-operated calcium entry (SOCE) in vascular smooth muscle cells (VSMCs) has not been fully characterized. Because sphingolipids and Ca(2+) modulate proliferation and constriction in VSMCs, characterizing the connection between S1P and SOCE may provide novel therapeutic targets for vascular diseases. We found that S1P triggered STIM1 puncta formation and SOCE in VSMCs. S1P-activated SOCE was inhibited by 2-aminoethoxydiphenyl borate (2-APB), diethylstilbestrol (DES), and gadolinium (Gd(3+)). SOCE was observed in VSMCs lacking either S1P(2) or S1P(3) receptors, suggesting that S1P acts via multiple signaling pathways. Indeed, both extracellular and intracellular S1P application increased the total internal reflection fluorescence signal in VSMCs cells transfected with STIM1-yellow fluorescent protein in a 2-APB-sensitive manner. These data, and the fact that 2-APB, DES, and Gd(3+) all inhibited S1P-induced cerebral artery constriction, suggest that SOCE modulates S1P-induced vasoconstriction in vivo. Finally, S1P-induced SOCE was larger in proliferative than in contractile VSMCs, correlating with increases in STIM1, Orai1, S1P(1), and S1P(3) receptor mRNA. These data demonstrate that S1P can act through both receptors and a novel intracellular pathway to activate SOCE. Because S1P-induced SOCE contributes to vessel constriction and is increased in proliferative VSMCs, it is likely that S1P/SOCE signaling in proliferative VSMCs may play a role in vascular dysfunction such as atherosclerosis and diabetes. PMID:21270296

  17. P/2008 CL94 (Lemmon) and P/2011 S1 (Gibbs): comet-like activity at large heliocentric distances

    NASA Astrophysics Data System (ADS)

    Kulyk, I.; Korsun, P.; Rousselot, P.; Afanasiev, V.; Ivanova, O.

    2016-06-01

    Based on spectroscopic and photometric observations we analyzed the dust environment of two minor distant objects, P/2008 CL94 (Lemmon) and P/2011 S1 (Gibbs). Both targets demonstrated the comet-like activity beyond the "zone of water-ice sublimation". Meanwhile the spectrum of P/2008 CL94 (Lemmon) did not reveal molecular emission features above reflected continuum in a spectral region of 4100-6800Å. Reddening of the continuum is linear along the dispersion with the mean normalized reflectivity gradient equals to 2.0% ± 0.4%. The normalized reflectivity of P/2011 S1 (Gibbs) derived from the V-R and R-I color indices equals 11% ± 9% and 26% ± 6% respectively. Both objects have likely small nuclei (about 2 and 4 km in the radii for P/2008 CL94 and P/2011 S1 respectively), which are consistent with nucleus sizes of 'Jupiter-family' comets. The level of physical activity of P/2008 CL94 and S/2011 S1 is characterized by R-Afρ quantity of 106 ± 3 cm and 76 ± 8 cm respectively. The Afρ values are resulted in dust production rates of about 1-2 kg/s, assuming the average geometric albedo of grains of 0.1 and the dust outflow velocities between 1 and 10 m/s.

  18. Isolation of Endogenously Assembled RNA-Protein Complexes Using Affinity Purification Based on Streptavidin Aptamer S1

    PubMed Central

    Dong, Yangchao; Yang, Jing; Ye, Wei; Wang, Yuan; Ye, Chuantao; Weng, Daihui; Gao, Huan; Zhang, Fanglin; Xu, Zhikai; Lei, Yingfeng

    2015-01-01

    Efficient isolation of endogenously assembled viral RNA-protein complexes is essential for understanding virus replication mechanisms. We have developed an affinity purification strategy based on an RNA affinity tag that allows large-scale preparation of native viral RNA-binding proteins (RBPs). The streptavidin-binding aptamer S1 sequence was inserted into the 3′ end of dengue virus (DENV) 5′–3′ UTR RNA, and the DENV RNA UTR fused to the S1 RNA aptamer was expressed in living mammalian cells. This allowed endogenous viral ribonucleoprotein (RNP) assembly and isolation of RNPs from whole cell extract, through binding the S1 aptamer to streptavidin magnetic beads. Several novel host DENV RBPs were subsequently identified by liquid chromatography with tandem mass spectrometry (LC-MS/MS), including RPS8, which we further implicate in DENV replication. We proposed efficient S1 aptamer-based isolation of viral assembled RNPs from living mammalian cells will be generally applicable to the purification of high- and low-affinity RBPs and RNPs under endogenous conditions. PMID:26389898

  19. Effect of electron correlation and shape resonance on photoionization from the S1 and S2 states of pyrazine

    NASA Astrophysics Data System (ADS)

    Suzuki, Yoshi-Ichi; Suzuki, Toshinori

    2012-11-01

    In a previous study [T. Horio, T. Fuji, Y.-I. Suzuki, and T. Suzuki, J. Am. Chem. Soc. 131, 10392 (2009), 10.1021/ja904780b], we demonstrated that the time-energy map of photoelectron angular anisotropy enables unambiguous identification of ultrafast S2(ππ*)-S1(nπ*) internal conversion in pyrazine. A notable characteristic of this map is that the forbidden ionization process of D0(n-1) ← S2(ππ*) gives a negative photoelectron anisotropy parameter. In the present study, we elucidate the mechanism of this process by calculating the photoionization transition dipole moments and photoelectron angular distribution using the first-order configuration interaction method and the continuum multiple scattering Xα approximation; these calculations at the S0 equilibrium geometry reproduce the observed anisotropy parameters for D0 ← S2 and D0 ← S1 ionizations, respectively. On the other hand, they do not reproduce the small difference in the photoelectron anisotropy parameters for the D1(π-1) ← S2 and D0 ← S1 ionizations, both of which correspond to removal of an electron from the same π* orbital in the excited states. We show that these ionizations are affected by the kag shape resonance and that the difference between their photoelectron anisotropy parameters originates from the difference in the molecular geometry in D1 ← S2 and D0 ← S1.

  20. Near infrared rubidium 62P3/2,1/2→62S1/2 laser

    NASA Astrophysics Data System (ADS)

    Moran, Paul J.; Richards, Ryan M.; Rice, Christopher A.; Perram, Glen P.

    2016-09-01

    An optically pumped near infrared rubidium (Rb) pulsed, mirrorless laser has been demonstrated in a heat pipe along both the 62P3/2-62S1/2 transition at 2.73 μm and the 62P1/2-62S1/2 transition at 2.79 μm. The bleached limit, slope efficiency, and maximum laser output energy of the near infrared Rb laser scale linearly with increasing Rb density, contrary to prior results. Previously, a maximum output energy of ~5 nJ had been observed before a rollover occurred in the scaling of output energy with rubidium concentration. In this experiment, the maximum laser output energy observed was ~100 nJ, with no indication of any scaling limitation. A maximum slope efficiency of 1.7×10-4 was observed. A small percentage of the pump photons were absorbed even at the maximum Rb density attainable in the heat pipe, indicating that laser efficiency could be scaled to near the quantum efficiency. Additionally, the hyperfine structure and absorption spectral profile of the 52S1/2-62P1/2 and 52S1/2-62P3/2 (blue) pump transitions were studied using a cw pump source.

  1. S1 nerve is the most efficient nerve rootlet innervating the anal canal and rectum in rats

    PubMed Central

    Fu, Kai; Luo, Pengbo; Zheng, Xianyou; Zhu, Xiaozhong; Wang, Lei; Chai, Yimin

    2015-01-01

    Autonomic and somatic components participate in the defecation process in mammals, combining signals from the brainstem and forebrain. The innervation pattern involved in micturition in rats has been well studied, while defecation has been less studied. The aim of the present study was to identify the most important sensory and motor nerves of the anal canal and rectum involved in defecation. The amplitudes of evoked potential of the anal canal and rectum were higher when L6 and S1 ventral rootlets were stimulated, compared with the other segments (ANOVA and Tukey’s post hoc test, all P < 0.05). The S1 segment was more strongly cholera toxin subunit B conjugated to horseradish peroxidase (CB-HRP) positive compared with the other segments (ANOVA and Tukey’s post hoc test, P < 0.05). Ventral spinal rootlets of L6 and S1 mainly contributed to the pressure change in the anal canal and rectum when the ventral spinal rootlets from L5 to S3 were stimulated electrically. In conclusion, many afferent and efferent nerves innervate the anal canal and rectum and are involved in defecation, but the S1 nerve rootlet could be the most efficient one. These results could provide a basis for defecation reconstruction, especially for patients with spinal cord injuries. PMID:26260583

  2. Short-time-scale variability in ventilation and export productivity during the formation of Mediterranean sapropel S1

    NASA Astrophysics Data System (ADS)

    Jilbert, Tom; Reichart, Gert-Jan; Mason, Paul; de Lange, Gert J.

    High-resolution laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) scanning of laminated sediments from the Urania basin is used to investigate short-time-scale variability in export productivity and redox conditions during the formation of eastern Mediterranean sapropel S1. Sedimentary enrichments of molybdenum (Mo), vanadium (V), and uranium (U) reflect deep-water redox conditions, most likely those near to the seawater-brine interface, while enrichment of Ba is related to biogenic barite and hence to export productivity. The enrichments of all four elements show strong variability on multidecadal to multicentennial time scales throughout S1. A partial decoupling of export productivity from redox conditions at the height of sapropel formation suggests that hydrographic changes, i.e., a variable ventilation rate of the eastern Mediterranean, played an important role in determining deep-water redox conditions. A pronounced switch is observed in the enrichments of redox-sensitive trace metals, from dominantly 300-600 year variability during early S1 to dominantly 100-300 year variability during late S1, indicating a change in the mean frequency of variability in the ventilation rate. The presence of a similar shift in the frequency of tropical and extratropical climate records at this time suggests that ventilation of the eastern Mediterranean was coupled to global climate variability.

  3. The cooperative role of S1P3 with LYVE-1 in LMW-HA-induced lymphangiogenesis.

    PubMed

    Yu, Mengsi; Zhang, Huizhen; Liu, Yiwen; He, Yiqing; Yang, Cuixia; Du, Yan; Wu, Man; Zhang, Guoliang; Gao, Feng

    2015-08-01

    Lymphangiogenesis, the formation of new lymph vessels, plays a significant role in the development and metastasis of various cancers. We and others have demonstrated that low molecular weight hyaluronan (LMW-HA) promotes lymphangiogenesis. However, the underlying mechanisms are poorly defined. In this study, using immunofluorescence and co-immunoprecipitation, we found that LMW-HA increased the colocalization of lymphatic vessel endothelial HA receptor (LYVE-1) and sphingosine 1-phosphate receptor (S1P3) at the cell surface. Silencing of either LYVE-1 or S1P3 decreased LMW-HA-mediated tube formation in lymphatic endothelial cells (LECs). Furthermore, silencing of either LYVE-1 or S1P3 significantly inhibited LMW-HA-induced tyrosine phosphorylation of Src kinase and extracellular signal-regulated kinase (ERK1/2). In summary, these results suggest that S1P3 and LYVE-1 may cooperate to play a role in LMW-HA-mediated lymphangiogenesis. This interaction may provide a useful target for the intervention of lymphangiogenesis-associated tumor progression. PMID:26116468

  4. 153. ARAIII Reactor building (ARA608) Foundation plan. Aerojetgeneral 880area/GCRE608S1. Date: ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    153. ARA-III Reactor building (ARA-608) Foundation plan. Aerojet-general 880-area/GCRE-608-S-1. Date: February 1958. Ineel index code no. 063-0608-60-013-102653. - Idaho National Engineering Laboratory, Army Reactors Experimental Area, Scoville, Butte County, ID

  5. Optical properties of ZnS1-xSex alloys fabricated by plasma-induced isoelectronic substitution

    NASA Astrophysics Data System (ADS)

    Rujkorakarn, Rong; Nelson, Art J.

    2000-06-01

    Nonequilibrium growth of thin-film ternary ZnS1-xSex semiconductor alloys was accomplished using physical vapor deposition with simultaneous electron cyclotron resonance H2S plasma activation. Substrate temperature, gas flow, and plasma power determine the ZnS1-xSex alloy composition and structure. Integrated optical transmission spectra for the ZnS1-xSex semiconductor alloys as a function of H2S plasma power are presented. Using the α2 vs hν plots for the various ZnS1-xSex films, the optical band gap Eg is extrapolated from each curve. This methodology yields the values of the band gap as a function of stoichiometry. We observe that the plasma induced isoelectronic substitution of S into the ZnSe lattice increases the band gap. This study shows that plasma-induced isoelectronic substitution is technologically feasible and useful for fabricating ternary II-VI alloys under nonequilibrium conditions.

  6. Isolation of Endogenously Assembled RNA-Protein Complexes Using Affinity Purification Based on Streptavidin Aptamer S1.

    PubMed

    Dong, Yangchao; Yang, Jing; Ye, Wei; Wang, Yuan; Ye, Chuantao; Weng, Daihui; Gao, Huan; Zhang, Fanglin; Xu, Zhikai; Lei, Yingfeng

    2015-01-01

    Efficient isolation of endogenously assembled viral RNA-protein complexes is essential for understanding virus replication mechanisms. We have developed an affinity purification strategy based on an RNA affinity tag that allows large-scale preparation of native viral RNA-binding proteins (RBPs). The streptavidin-binding aptamer S1 sequence was inserted into the 3' end of dengue virus (DENV) 5'-3' UTR RNA, and the DENV RNA UTR fused to the S1 RNA aptamer was expressed in living mammalian cells. This allowed endogenous viral ribonucleoprotein (RNP) assembly and isolation of RNPs from whole cell extract, through binding the S1 aptamer to streptavidin magnetic beads. Several novel host DENV RBPs were subsequently identified by liquid chromatography with tandem mass spectrometry (LC-MS/MS), including RPS8, which we further implicate in DENV replication. We proposed efficient S1 aptamer-based isolation of viral assembled RNPs from living mammalian cells will be generally applicable to the purification of high- and low-affinity RBPs and RNPs under endogenous conditions. PMID:26389898

  7. Interrelation between optical, refractometric, and lattice parameters of Cu6P(S1- x Sex)5I crystals

    NASA Astrophysics Data System (ADS)

    Studenyak, I. P.; Suslikov, L. M.; Kovacs, Gy. Sh.; Kranjčec, M.; Tovt, V. V.

    2001-04-01

    The influence of the compositional disordering on the energy of the fundamental absorption edge and the refractive index dispersion of the crystalline solid solutions Cu6P(S1- x Sex)5I is studied. It is shown that the concentration dependences of the optical pseudogap width, the refractive index, and the lattice parameter in these crystalline solid solutions are interrelated.

  8. SKI-1/S1P inhibition: a promising surrogate to statins to block hepatitis C virus replication.

    PubMed

    Blanchet, Matthieu; Seidah, Nabil G; Labonté, Patrick

    2012-08-01

    Hepatitis C virus (HCV) is often associated with steatosis, cirrhosis and hepatocellular carcinoma (HCC). Statins (HMG-CoAR inhibitors) have been shown to exert an antiviral effect in vitro, principally on replicon harboring cells, but the effect of their use alone in vivo remains controversial. In clinical trials, when used in combination with the standards of care (SOC), they led to an increased proportion of sustained virological responder (SVR). Here we investigated the implication of SKI-1/S1P, a master lipogenic pathways regulator upstream of HMG-CoAR, on different steps of HCV life cycle. We compared the HCV antiviral effect of the most potent SKI-1/S1P small molecule inhibitor (PF-429242) with a set of two statins on different steps of the viral life cycle, and showed that SKI-1/S1P inhibitor blocked HCVcc (strain JFH-1) RNA replication (EC(50)= 5.8 μM) more efficiently than statins. Moreover, we showed that PF-429242 could reduce lipid droplets accumulation in Huh7 cells. Interestingly, PF-429242 dramatically reduced infectious particles production (EC(90)= 4.8 μM). Such inhibition could not be achieved with statins. SKI-1/S1P activity is thus essential for viral production and its inhibition should be considered for antiviral drug development. PMID:22626636

  9. 40 CFR Table S-1 to Subpart S of... - Basic Parameters for the Calculation of Emission Factors for Lime Production

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Basic Parameters for the Calculation of Emission Factors for Lime Production S Table S-1 to Subpart S of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING...

  10. 40 CFR Table S-1 to Subpart S of... - Basic Parameters for the Calculation of Emission Factors for Lime Production

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Basic Parameters for the Calculation of Emission Factors for Lime Production S Table S-1 to Subpart S of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING...

  11. 40 CFR Table S-1 to Subpart S of... - Basic Parameters for the Calculation of Emission Factors for Lime Production

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Basic Parameters for the Calculation of Emission Factors for Lime Production S Table S-1 to Subpart S of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING...

  12. 40 CFR Table S-1 to Subpart S of... - Basic Parameters for the Calculation of Emission Factors for Lime Production

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Basic Parameters for the Calculation of Emission Factors for Lime Production S Table S-1 to Subpart S of Part 98 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) MANDATORY GREENHOUSE GAS REPORTING...

  13. Registration of the maize germplasm CRW3(S1)C6 with resistance to western corn rootworm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maize germplasm CRW3(S1)C6 is a synthetic population developed with resistance to western corn rootworm (WCR) by the USDA-ARS Plant Genetics Research Unit in cooperation with the Missouri Agricultural Experiment Station at the University of Missouri-Columbia. The corn rootworm is one of the most se...

  14. 144. ARAIII Control building (ARA607) Foundation plan. Aerojetgeneral 880area/GCRE607S1. Date: ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    144. ARA-III Control building (ARA-607) Foundation plan. Aerojet-general 880-area/GCRE-607-S-1. Date: February 1958. Ineel index code no. 063-0607-60-013-102568. - Idaho National Engineering Laboratory, Army Reactors Experimental Area, Scoville, Butte County, ID

  15. Anomalie d’émergence radiculaire par racine conjointe S1: à propos d'un cas

    PubMed Central

    Kessely, Yannick Canton; Sakho, Maguette Gaye; Fondo, Alidji; Daisy, Akerey Diop; Thiam, Aley; Sakho, Youssoupha

    2015-01-01

    De découverte per-opératoire pour hernie discale, les anomalies d’émergence radiculaires constituent une entité rare. La présentation clinique est généralement identique à celle d'une radiculopathie. Nous rapportons le cas d'un patient âgé de 35 ans présentant une sciatique droite S1 hyperalgique rebelle aux multiples médications. L'IRM du rachis lombo-sacré avait mis en évidence une discopathie protrusive de petit volume en L5 S1 droite et un aspect de grosse racine ou de kyste de Tarlov au niveau de l’émergence droite de S1. Une fenestration inter lamaire L5-S1 droite avec une ablation du ligament jaune a montré une émergence radiculaire double au niveau de l'espace retro-discal. Un geste de foraminostomie a été réalisé sans discectomie. L’évolution a très favorable avec une rétrocession dès le lendemain. L'analyse pré-opératoire fine et rigoureuse de l'imagerie est indispensable. Une bonne libération améliore l’état clinique du patient. Y penser en cas de sciatique hyperalgique sans Lasègue. PMID:26113909

  16. The preS1 antigen of hepatitis B virus is highly immunogenic at the T cell level in man.

    PubMed Central

    Ferrari, C; Penna, A; Bertoletti, A; Cavalli, A; Valli, A; Schianchi, C; Fiaccadori, F

    1989-01-01

    14 hepatitis B vaccine recipients who showed high titers of anti-hepatitis B surface antibodies in serum after booster immunization with a polyvalent hepatitis B surface antigen vaccine that contained trace amounts of hepatitis B virus (HBV) preS1 and preS2 envelope antigens were studied for their in vitro T cell response to these antigens. All 14 subjects displayed a significant proliferative T cell response to the S/p25 envelope region encoded polypeptide; 8 also responded to preS1, while only 1 showed a significant level of T cell proliferation to preS2. Limiting dilution analysis demonstrated that the frequency of preS-specific T cells in two of these vaccine recipients was higher than that of S/p25-specific T cells. T cell cloning was then performed and a total of 29 HBV envelope antigen-reactive CD4+ cloned lines were generated from two preS-responsive vaccines. 21 of these lines were S/p25 specific, 7 preS1 specific, and 1 preS2 specific. Taken together, all these results suggest that the preS1 antigen may function as a strong T cell immunogen in man. PMID:2529268

  17. Effect of CSN1S1-CSN3 (α(S1)-κ-casein) composite genotype on milk production traits and milk coagulation properties in Mediterranean water buffalo.

    PubMed

    Bonfatti, V; Giantin, M; Gervaso, M; Coletta, A; Dacasto, M; Carnier, P

    2012-06-01

    The aim of this study was to estimate effects of CSN1S1-CSN3 (α(S1)-κ-casein) composite genotypes on milk production traits and milk coagulation properties (MCP) in Mediterranean water buffalo. Genotypes at CSN1S1 and CSN3 and coagulation properties [rennet clotting time (RCT), curd firming time (K₂₀), and curd firmness (A₃₀)] were assessed by reversed-phase HPLC and computerized renneting meter analysis, respectively, using single test-day milk samples of 536 animals. Alternative protein variants of α(S1)-CN and κ-CN were detected by HPLC, and identification of the corresponding genetic variants was carried out by DNA analysis. Two genetic variants were detected at CSN1S1 (A and B variants) and 2 at CSN3 (X1 and X2 variants). Statistical inference was based on a linear model including the CSN1S1-CSN3 composite genotype effect (7 genotypes), the effects of herd-test-day (8 levels), and a combined days in milk (DIM)-parity class. Composite genotype AB-X2X2 was associated with decreased test-day milk yield [-0.21 standard deviation (SD) units of the trait] relative to genotype BB-X2X2. Genotypes did not affect milk protein content, but genotype AB-X1X1 was associated with increased fat content compared with genotype BB-X2X2 (+0.28 SD units of the trait) and AB-X1X1 (+0.43 SD units of the trait). For RCT, the largest difference (+1.91 min; i.e., 0.61 SD units of the trait) was observed between genotype AA-X1X2 and AB-X1X1. Direction of genotype effects on K(20) was consistent with that for RCT. The maximum variation in K₂₀ due to genotype effects (between AA-X1X2 and AB-X1X1 genotypes) was almost 0.9 SD units of the trait. Magnitude of genotype effects was smaller for A₃₀ than for RCT and K₂₀, with a maximum difference of 0.5 SD units of the trait between genotype AA-X1X2 and AA-X1X1. The B allele at CSN1S1 was associated with increased RCT and K₂₀ and with weaker curds compared with allele A. Allele X2 at CSN3 exerted opposite effects on

  18. A Meta-analysis Reveals S-1-based Chemotherapy Improves the Survival of Patients With Advanced Gastric Cancer.

    PubMed

    Wu, Fang-Lan; Lu, De-Cheng; Ying, Yan-Ping; Huang, Jin-Jiao; Zhou, Ai-Min; Jiang, Dun-Ke; Chen, Mao-Wei; Yang, Xi; Zhou, Jia; Huang, Hui-Qiao; Zeng, Hong-Yan

    2015-04-01

    The aim of this study was to compare the efficacy and safety of S-1-based therapy versus non-S-1-based therapy in advanced gastric cancer (AGC) patients.Eligible studies stratifying objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) in AGC patients were identified from Embase, Pubmed, Cochrane Library, and China National Knowledge Infrastructure databases. The STATA package (version 11.0) was used to pool the data from the eligible studies.Fifteen studies with 2973 AGC cases, of which 1497 (50.4%) received S-1-based therapy and 1476 (49.6%) received non-S-1-based therapy, were identified in the meta-analysis. AGC patients who had received S-1-based therapy had a higher median OS, median PFS, and ORR than those who had received 5-fluorouracil (FU)-based therapy (OS: hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80-0.98, P = 0.015; PFS: HR 0.88, 95% CI 0.80-0.98, P = 0.016; ORR: OR 1.25, 95% CI 1.08-1.45, P = 0.003, respectively). S-1-based therapy had similar efficacy to capecitabine-based therapy in terms of median OS (HR 1.14, 95% CI 0.91-1.41, P = 0.253), median PFS (HR 1.01, 95% CI 0.82-1.25, P = 0.927), and ORR (OR 0.84, 95% CI 0.63-1.12, P = 0.226). Subgroup analysis for grade 3 to 4 toxicity showed higher incidence of neutropenia (relative risk [RR] = 0.827, P = 0.006), nausea (RR = 0.808, P = 0.040), and lower diarrhea (RR = 1.716, P = 0.012) in 5-FU-based arm, and higher diarrhea (RR = 0.386, P = 0.007) in capecitabine-based arm.S-1-based chemotherapy is favorable to AGC patients with better clinical benefit than 5-FU-based chemotherapy and with equivalent antitumor compare with capecitabine-based therapy. PMID:25906091

  19. Structure of conkunitzin-S1, a neurotoxin and Kunitz-fold disulfide variant from cone snail

    SciTech Connect

    Dy, Catherine Y.; Buczek, Pawel; Imperial, Julita S.; Bulaj, Grzegorz; Horvath, Martin P.

    2006-09-01

    Most Kunitz proteins like BPTI and α-dendrotoxin are stabilized by three disulfide bonds. The crystal structure shows how subtle repacking of non-covalent interactions may compensate for disulfide bond loss in a naturally occurring two-disulfide variant, conkunitzin-S1, the first discovered member of a new conotoxin family. Cone snails (Conus) are predatory marine mollusks that immobilize prey with venom containing 50–200 neurotoxic polypeptides. Most of these polypeptides are small disulfide-rich conotoxins that can be classified into families according to their respective ion-channel targets and patterns of cysteine–cysteine disulfides. Conkunitzin-S1, a potassium-channel pore-blocking toxin isolated from C. striatus venom, is a member of a newly defined conotoxin family with sequence homology to Kunitz-fold proteins such as α-dendrotoxin and bovine pancreatic trypsin inhibitor (BPTI). While conkunitzin-S1 and α-dendrotoxin are 42% identical in amino-acid sequence, conkunitzin-S1 has only four of the six cysteines normally found in Kunitz proteins. Here, the crystal structure of conkunitzin-S1 is reported. Conkunitzin-S1 adopts the canonical 3{sub 10}–β–β–α Kunitz fold complete with additional distinguishing structural features including two completely buried water molecules. The crystal structure, although completely consistent with previously reported NMR distance restraints, provides a greater degree of precision for atomic coordinates, especially for S atoms and buried solvent molecules. The region normally cross-linked by cysteines II and IV in other Kunitz proteins retains a network of hydrogen bonds and van der Waals interactions comparable to those found in α-dendrotoxin and BPTI. In conkunitzin-S1, glycine occupies the sequence position normally reserved for cysteine II and the special steric properties of glycine allow additional van der Waals contacts with the glutamine residue substituting for cysteine IV. Evolution has thus defrayed

  20. Human aquaporin 4 gating dynamics in dc and ac electric fields: A molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Garate, J.-A.; English, Niall J.; MacElroy, J. M. D.

    2011-02-01

    Water self-diffusion within human aquaporin 4 has been studied using molecular dynamics (MD) simulations in the absence and presence of external ac and dc electric fields. The computed diffusive (pd) and osmotic (pf) permeabilities under zero-field conditions are (0.718 ± 0.24) × 10-14 cm3 s-1 and (2.94 ± 0.47) × 10-14 cm3 s-1, respectively; our pf agrees with the experimental value of (1.50 ± 0.6) × 10-14 cm3 s-1. A gating mechanism has been proposed in which side-chain dynamics of residue H201, located in the selectivity filter, play an essential role. In addition, for nonequilibrium MD in external fields, it was found that water dipole orientation within the constriction region of the channel is affected by electric fields (e-fields) and that this governs the permeability. It was also found that the rate of side-chain flipping motion of residue H201 is increased in the presence of e-fields, which influences water conductivity further.

  1. Phase II Study of Preoperative Concurrent Chemoradiation Therapy With S-1 in Patients With T4 Oral Squamous Cell Carcinoma

    SciTech Connect

    Nomura, Tomoko; Murakami, Ryuji; Toya, Ryo; Teshima, Keiko; Nakahara, Aya; Hirai, Toshinori; Hiraki, Akimitsu; Nakayama, Hideki; Yoshitake, Yoshihiro; Ota, Kazutoshi; Obayashi, Takehisa; Yamashita, Yasuyuki; Oya, Natsuo; Shinohara, Masanori

    2010-04-15

    Purpose: To determine the feasibility and efficacy of preoperative concurrent chemoradiation therapy (CCRT) with S-1, an oral fluoropyrimidine derivative, in patients with T4 oral squamous cell carcinoma (SCC). Methods and Materials: Only patients with histologically proven T4 oral SCC were included. Radiotherapy (total dose, 30 Gy) was delivered in 2-Gy daily fractions over a period of 3 weeks. Concurrently, S-1 (80 mg/m{sup 2}/day) was administered orally twice daily for 14 consecutive days. Results: We enrolled 46 patients. All underwent radiotherapy as planned; however, oral S-1 was discontinued in 3 patients who manifested acute toxicity. Grade 3 toxicities were mucositis (20%), anorexia (9%), and neutropenia (4%). We encountered no Grade 4 adverse events or serious postoperative morbidity requiring surgical intervention. After CCRT, 32 of the 46 patients underwent radical resection; in 17 (53%) of the operated patients, the pathologic response was complete. During follow-up ranging from 7 to 58 months (median, 22 months), tumor control failed in 5 (16%) of the 32 operated patients; there were 3 local and 2 regional failures. Of the 14 non-operated patients, 8 (57%) manifested local (n = 7) or regional failure (n = 1). The 3-year overall survival rate for all 46 patients was 69%; it was significantly higher for operated than for non-operated patients (82% vs. 48%; p = 0.0288). Conclusion: Preoperative CCRT with S-1 is feasible and effective in patients with T4 oral SCC. Even in inoperable cases, CCRT with S-1 provides adequate tumor control.

  2. FTY720P inhibits hepatic Na(+)-K(+) ATPase via S1PR2 and PGE2.

    PubMed

    Al Alam, Nadine; Kreydiyyeh, Sawsan Ibrahim

    2016-08-01

    Sphingosine-1-phosphate (S1P) was found previously to inhibit Na(+)-K(+) ATPase in HepG2 cells. Whether fingolimod (FTY720), a S1P receptor (S1PR) agonist, similarly inhibits the ATPase is a question that needs to be addressed. The aim of this work was to study the effect of FTY720P, the active form of the drug, on the activity of Na(+)-K(+) ATPase in HepG2 cells and determine its mechanism of action. The activity of the ATPase was assayed by measuring the amount of inorganic phosphate liberated in the presence and the absence of ouabain. FTY720-P (7.5 nmol/L, 15 min) significantly reduced the activity of the ATPase. This effect disappeared completely in the presence of JTE-013, which is a specific blocker of sphingosine-1-phosphate receptor 2 (S1PR2), as well as in the presence of calphostin and indomethacin, which are inhibitors of protein kinase C (PKC) and COX-2, respectively. The effect of FTY720P was mimicked by prostaglandin E2 (PGE2) and PMA, but abrogated by NF-κB inhibition. When NF-κB was inhibited, the effect of exogenous PGE2 still appeared, but that of PMA did not manifest, suggesting that NF-κB is upstream of PGE2 and downstream of PKC. It was concluded that FTY720P activates via S1PR2, PKC, and NF-κB. The latter induces PGE2 generation and inhibits Na(+)-K(+) ATPase. PMID:27501354

  3. Changes in Neuroforaminal Height with 2 Level Axial Presacral Lumbar Interbody Fusion at L4-S1

    PubMed Central

    Marawar, Satyajit; Jung, Jin; Sun, Mike

    2014-01-01

    Background The objective was to examine the changes in neuroforaminal height at L4-L5 and L5-S1 after insertion and graduated foraminal distraction using the 2 level transsacral implant in a cadaveric model. Methods Discectomy and transsacral instrumentation was performed in six fresh human cadavers at L4-S1. The neuroforaminal height was measured at L4-L5 and L5-S1 before and after insertion of the implant and then at each stage of manual distraction. Results Mean L4-5 neuroforaminal height increased from 18.2 ± 3.1mm to 20.3± 2.9mm (11%) on the left and from 18.8±2.8mm to 20.6± 2.3mm (12%) on the right (P<0.05). Mean L5-S1 neuroforaminal height increased from 15.7±3.0mm to 18.4 ±2.8mm (17%) on the left and from 15.6 ±2.1mm to 18.3 ±1.8mm (17%) on the right (P<0.05). When the neuroforaminal height was plotted against amount of rotation of the screw driver it was found that the neuroforaminal height at L5-S1 increased by 1mm on average for every complete revolution of the screw driver. At least 2 full rotations of the screw driver were achieved in all cadavers. Conclusions The transsacral screw construct distracted the disc space and neuroforaminal height in a cadaveric spine model without soft tissue envelope. During the initial process, manual control of disc space distraction predictably correlated with the increase in the neuroforaminal height to a maximum. However, further research is needed to look at variables affecting disc space pliability, implant subsidence, in vivo application, and clinical benefit of this procedure. PMID:25694937

  4. Phase I Study of Preoperative Chemoradiation With S-1 and Oxaliplatin in Patients With Locally Advanced Resectable Rectal Cancer

    SciTech Connect

    Hong, Yong Sang; Lee, Jae-Lyun; Park, Jin Hong; Kim, Jong Hoon; Yoon, Sang Nam; Lim, Seok-Byung; Yu, Chang Sik; Kim, Mi-Jung; Jang, Se-Jin; Lee, Jung Shin; Kim, Jin Cheon; Kim, Tae Won

    2011-03-01

    Purpose: To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose. Methods and Materials: Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m{sup 2}/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m{sup 2}/day, gradually increasing to 60, 70, and 80 mg/m{sup 2}/day. Surgery was performed within 6 {+-} 2 weeks. Results: Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m{sup 2}/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%). Conclusions: The recommended dose of S-1 was determined to be 80 mg/m{sup 2}/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.